Rate-corrected QT Research Articles

Predicting long-term risk of sudden cardiac death with automatic computer-interpretations of electrocardiogram.

Computer-interpreted electrocardiogram (CIE) data is provided by almost all commercial software used to capture and store digital electrocardiograms. CIE is widely available, inexpensive, and accurate. We tested the potential of CIE in long-term sudden cardiac death (SCD) risk prediction. This is a retrospective of 8,568 consecutive patients treated for acute coronary syndrome. The primary endpoint was five-year occurrence of SCDs or equivalent events (SCDs aborted by successful resuscitation or adequate ICD therapy). CIE statements were extracted from summary statements and measurements made by the GE Muse 12SL algorithm from ECGs taken during admission. Three supervised machine learning algorithms (logistic regression, extreme gradient boosting, and random forest) were then used for analysis to find risk features using a random 70/30% split for discovery and validation cohorts. Five-year SCD occurrence rate was 3.3% (n = 287). Regardless of the used ML algorithm, the most significant risk ECG risk features detected by the CIE included known risk features such as QRS duration and factors associated with QRS duration, heart rate-corrected QT time (QTc), and the presence of premature ventricular contractions (PVCs). Risk score formed by using most significant CIE features associated with the risk of SCD despite adjusting for any clinical risk factor (including left ventricular ejection fraction). Sensitivity of CIE data to correctly identify patients with high risk of SCD (over 10% 5-year risk of SCD) was usually low, but specificity and negative prediction value reached up to 96.9% and 97.3% when selecting only the most significant features identified by logistic regression modeling (p-value threshold <0.01 for accepting features in the model). Overall, CIE data showed a modest overall performance for identifying high risk individuals with area under the receiver operating characteristic curve values ranging between 0.652 and 0.693 (highest for extreme gradient boosting and lowest for logistic regression). This proof-of-concept study shows that automatic interpretation of ECG identifies previously validated risk features for SCD.

Safety of single-dose bedaquiline combined with rifampicin for leprosy post-exposure prophylaxis: A Phase 2 randomized non-inferiority trial in the Comoros Islands.

To reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP). From July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) <450 ms and liver enzyme tests (ALT/AST) below 3× the upper limit of normal (ULN), before they were individually randomized 1:1 in an open-label design. Recruitment was sequential, by age group. Pediatric dosages were weight adjusted. Follow-up was done at day 1 post-dose (including ECG) and day 14 (including ALT/AST), with repeat of ALT/AST on the last follow-up at day 30 in case of elevation on day 14. The primary outcome was non-inferiority of BE-PEP based on a <10 ms difference in QTc 24 h after treatment administration, both unadjusted and adjusted for baseline QTc. Of 408 screened participants, 313 were enrolled, starting with 187 adults, then 38 children aged 13 to 17 years, and finally 88 children aged 5 to 12 years, of whom 310 (99%) completed all visits. Across all ages, the mean QTc change on BE-PEP was from 393 ms to 396 ms, not significantly different from the change from 392 ms to 394 ms on SDR-PEP (difference between arms 1.8 ms, 95% CI -1.8, 5.3, p = 0.41). No individual's QTc increased by >50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; -1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group. In this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros. ClinicalTrials.gov NCT05406479.

Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants.

The combination of cagrilintide and semaglutide (CagriSema) is being developed for the treatment of obesity and type 2 diabetes. The objective of this thorough QT study was to confirm that cagrilintide does not result in a clinically relevant prolongation in cardiac repolarization compared with placebo. This was a double-blind study (NCT05804162) in which healthy participants were randomized to cagrilintide, administered as a once-weekly subcutaneous injection dose escalated to 4.5 mg, or a placebo. The primary end point was the time-matched change from baseline in Fridericia heart rate-corrected QT interval (QTcF) at 12-, 24-, 48- and 72 h after the last cagrilintide 4.5-mg dose. To conclude that cagrilintide does not induce a clinically relevant prolongation, the upper limit of the two-sided 90% confidence interval (CI) for the treatment difference at each of the four time points must fall below 10 ms. To establish QT assay sensitivity, participants in the placebo arms received a single 400-mg oral moxifloxacin dose as a positive control and moxifloxacin placebo in a nested cross-over fashion. A total of 105 participants received cagrilintide (n = 53) or placebo (n = 52). No clinically relevant QTcF prolongation occurred after the last cagrilintide 4.5-mg dose; the upper limits of the two-sided 90% CIs of the placebo-adjusted QTcF changes from baseline were below 10 ms at all time points. QT assay sensitivity was demonstrated with moxifloxacin as a positive control. Cagrilintide did not result in clinically relevant QTcF prolongation, indicating no increased risk of ventricular tachyarrhythmias.

Drug-induced QT interval prolongation in patients with heart failure with preserved ejection fraction.

Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced QT interval prolongation. It is unknown if HF with preserved ejection fraction (HFpEF) is also associated with an increased risk. Dofetilide and sotalol are potent QT interval-prolonging agents that are frequently used in patients with HFpEF, in whom atrial fibrillation is a common comorbidity. We tested the hypothesis that the risk of QT interval prolongation associated with dofetilide and sotalol is increased in patients with HFpEF. We conducted a retrospective cohort study conducted using electronic health records from the Indiana Network for Patient Care (January 31, 2010 -May 3, 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, and absence of QT interval records, we identified patients taking dofetilide or sotalol among three groups: HFrEF (n = 138), HFpEF (n = 109), and no HF (n = 729). QT prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy. Unadjusted odds ratios (OR) for QT prolongation were determined by univariate analysis. Adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates. QTc prolongation associated with dofetilide or sotalol occurred in 53.2%, 71.7% and 30.0% of patients with HFpEF, HFrEF, and patients with no HF, respectively. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of QTc prolongation were significantly higher in patients with HFpEF [OR = 1.98 (95% CI 1.17-3.33)], and in those with HFrEF [OR = 5.23, (3.15-8.67)], compared to those with no evidence of HF. The odds of QT prolongation among inpatients receiving dofetilide or sotalol were increased in patients with HFpEF and HFrEF compared to those who did not have HF.

A Calculated Risk: Evaluation of QTc Drug-Drug Interaction (DDI) Clinical Decision Support (CDS) Alerts and Performance of the Tisdale Risk Score Calculator.

A risk factor for a potentially fatal ventricular arrhythmia Torsade de Pointes is a prolongation in the heart rate-corrected QT interval (QTc) ≥ 500milliseconds (ms) or an increase of ≥60ms from a patient's baseline value, which can cause sudden cardiac death. The Tisdale risk score calculator uses clinical variables to predict which hospitalized patients are at the highest risk for QTc prolongation. To determine the rate of overridden QTc drug-drug interaction (DDI)-related clinical decision support (CDS) alerts per patient admission and the prevalence by Tisdale risk score category of these overridden alerts. Secondary outcome was to determine the rate of drug-induced QTc prolongation (diQTP) associated with overrides. Our organization's enterprise data warehouse was used to retrospectively access QTc DDI alerts presented for patients aged ≥18years who were admitted to Brigham and Women's Hospital during 2022. The QTc DDI CDS alerts were included if shown to a physician, fellow, resident, physician assistant, or nurse practitioner when entering the order in inpatient areas for patients with a length of stay of at least 2days. Variables collected for the Tisdale calculator included age, sex, whether patient was on a loop diuretic, potassium level, admission QTc value, admitting diagnosis of acute myocardial infarction, sepsis, or heart failure, and number of QTc-prolonging drugs given to the patient. A total of 2649 patients with 3033 patient admissions had 18,432 QTc DDI alerts presented that were overridden. An average of 3 unique QTc DDI alerts were presented per patient admission and the alerts were overridden an average of 6 times per patient admission. Overall, 6% of patient admissions were low risk (score ≤ 6), 64% moderate risk (score 7-10), and 30% high risk (score ≥ 11) of QTc prolongation. The most common QTc DDI alerts overridden resulting in an diQTP were quetiapine and propofol (11%) and amiodarone and haloperidol (7%). The diQTP occurred in 883 of patient admissions (29%) and was more frequent in those with higher risk score, with 46% of patient admissions with diQTP in high risk, 23% in moderate risk, and 8% in low risk. Use of the Tisdale calculator to assess patient-specific risk of QT prolongation combined with CDS may improve overall alert quality and acceptance rate, which may decrease the diQTP rate.

Association Between Disturbed Serum Phosphorus Levels and QT Interval Prolongation

INTRODUCTIONQT interval prolongation is a risk factor for fatal arrhythmias and other cardiovascular complications. QT interval prolongation in hemodialysis (HD) patients is not well understood. Hypocalcemia is a suspected, but poorly verified etiology in these patients, and the association between serum phosphorus levels and QT interval prolongation is unknown. We sought to determine the prevalence of QT interval prolongation in HD patients and to verify the association between pre-dialysis serum Ca and P levels and QT interval prolongation. METHODSA cross-sectional study was conducted on adult maintenance HD patients enrolled in the Japanese Society for Dialysis Therapy and Renal Data Registry 2019. After assessing patient characteristics, linear regression analysis was performed with pre-dialysis serum Ca and P levels as exposures and a rate-corrected QT (QTc) interval as the outcome. RESULTSA total of 204,530 patients were analyzed with a mean QTc of 451.2 msec (SD = 36.9 msec). On multivariable analysis, estimated change in QTc (coefficients, [95% confidence interval {CI}])] per 1 mg/dL increase in serum Ca and P was -2.02 [-3.00, -1.04] and 5.50 [3.92,7.09], respectively. In the restricted cubic spline curve, estimated change in QTc increased with lower values of serum Ca. The correlation between serum P and QTc showed a U-shaped curve. CONCLUSIONDecreased serum Ca levels and decreased and increased serum P levels may be associated with QT interval prolongation in maintenance HD patients.

QTc intervals at rest and during exercise assessed by group correction formulas in survivors of childhood acute lymphoblastic leukemia

IntroductionEarly signs of subclinical cardiac damage must be identified before they turn into clinical manifestations. Tailoring a formula is relevant for precise QTc evaluation in childhood acute lymphoblastic leukemia (ALL) survivors considering they are at risk of long-term cardiac problems. Therefore, we aim to develop group heart rate correction formulas for QT intervals in childhood ALL survivors at rest and during exercise, and to assess the applicability of these methods across a variety of risk groups exposed to diverse chemotherapy dosages. MethodsTwo hundred and fifty childhood ALL survivors in the PETALE study were classified into 3 groups depending on their prognostic risk group. ECG measurements (QT and RR intervals) were made at rest and during a cardiopulmonary exercise test. QT correction for heart rate was applied using 5 different formulas, which included 2 previously published formulas and 3 group-specific formulas for each sex. ResultsThe QT/RR relation showed 2 different curves between rest and during exercise, which was worse for females. Group-specific QTc formulas allowed adequate heart rate-corrected QT interval, independently of the cumulative dose of doxorubicin received during treatment. Group-specific formulas showed significantly shorter QTc intervals than QTc from Bazett's formula. QTc (Bazett's formula) values surpassed the established clinical norm in 22 males (11%) and 22 females (11%), with a majority occurring during exercise, affecting 15 males (7.5%) and 10 females (5%). ConclusionThis study shows the applicability of personalized group correction of QT/RR data in childhood ALL survivors. Our comprehensive assessments (spanning rest, exercise, and recovery) is an effective approach for risk stratification of cardiac complications in childhood ALL survivors.

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.

Effects of Anesthetics on Cardiac Repolarization in Adults: A Network Meta-Analysis of Randomized Clinical Trials.

Prolongation of cardiac repolarization, especially the heart rate-corrected QT (QTc) interval, is associated with life-threatening dysrhythmias. This study aimed to identify the anesthetic with the lowest risk of prolonging cardiac repolarization and provide guidance for anesthesia management in patients with cardiac diseases or long QT syndrome. Randomized controlled trials (RCTs) comparing the effects of anesthetics on cardiac repolarization indices were searched for in multiple databases. The primary outcome was QTc; and the secondary outcomes were other repolarization indices. A network meta-analysis was conducted using a frequentist approach and registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022304970). Thirteen RCTs investigating 953 adults with normal QTc interval and without cardiovascular diseases were included. Direct meta-analyses found that propofol had less influence than sevoflurane (95% confidence interval (CI): 16.10, 33.54) and desflurane (95% CI: 4.85, 35.36), and sevoflurane had less influence than desflurane (95% CI: 6.96, 19.39) on QTc prolongation. Network analysis found that propofol had less influence than sevoflurane (95% CI: 17.78, 29.63), halothane (95% CI: 11.29, 41.24), desflurane (95% CI: 23.79, 39.88), and isoflurane (95% CI: 20.11, 46.10), and sevoflurane had less influence than desflurane (95% CI: 0.43, 15.82) on QTc prolongation. The rank order of cumulative ranking curve analysis was propofol (100%), sevoflurane (63.8%), halothane (49.5%), desflurane (21.1%), and isoflurane (15.6%). The direct meta-analysis found that propofol had less influence than sevoflurane on QT prolongation (95% CI: 23.12, 57.86). Other secondary outcomes showed no conclusive findings. This meta-analysis found that propofol had a minimal effect on QTc prolongation, followed by sevoflurane and desflurane in adults with normal QTc interval and without cardiovascular diseases. Propofol is the best anesthetic for adult patients with long QT syndrome or cardiac diseases, but still needs more robust evidence.

Magnetocardiography at rest predicts cardiac death in patients with acute chest pain.

Sudden cardiac arrest is a major cause of morbidity and mortality worldwide and remains a major public health problem for which better non-invasive prediction tools are needed. Primary preventive therapies, such as implantable cardioverter defibrillators, are not personalized and not predictive. Most of these devices do not deliver life-saving therapy during their lifetime. The individual relationship between fatal arrhythmias and cardiac function abnormalities in predicting cardiac death risk has rarely been explored. We retrospectively analyzed the measurements at rest for 191 patients with acute chest pain (ACP) magnetocardiographically. Our recently introduced analyses are able to detect inhomogeneities of the depolarization and repolarization. Moreover, electrically silent phenomena-intracellular ionic currents as well as vortex currents-can be measured and quantified. All included ACP patients were recruited in 2009 at Yonsei University Hospital and were followed up until 2022. During half of the follow-up period (6.5 years), 11 patients died. Out of all the included nine clinical, eight magnetocardiographical, and nine newly introduced magnetoionographical parameters we tested in this study, three parameters revealed themselves to be outstanding at predicting death: heart rate-corrected QT (QTc) prolongation, depression of repolarization current IKr + IKs, and serum creatinine (all significant in Cox regression, p < 0.05). They clearly predicted cardiac death over the 6.5 years duration (sensitivity 90.9%, specificity 85.6%, negative predictive accuracy 99.4%). Cardiac death risk was more than ninefold higher in patients with low repolarization reserve and QTc prolongation in comparison with the remaining patients with ACP (p < 0.001). The non-parametric Kaplan-Meier statistics estimated significantly lower survival functions from their lifetime data (p < 0.001). To the best of our knowledge, these are the first data linking magnetocardiographical and magnetoionographical parameters and subsequent significant fatal events in people, suggesting structural and functional components to clinical life-threatening ventricular arrhythmogenesis. The findings support investigation of new prevention strategies and herald those new non-invasive techniques as complementary risk stratification tools.

Plastic additive components of PM2.5 increase corrected QT interval: Screening for exposure markers based on airborne exposome.

The impact of industrial chemical components of ambient fine particles (e.g. PM2.5) on cardiovascular health has been poorly explored. Our study reports for the first time the associations between human exposure to complex plastic additive (PA) components of PM2.5 and prolongation of heart rate-corrected QT (QTC) interval by employing a screening-to-validation strategy based on a cohort of 373 participants (136 in the screening set and 237 in the validation set) recruited from 7 communities across China. The high-throughput airborne exposome framework revealed ubiquitous occurrences of 95 of 224 target PAs in PM2.5, totaling from 66.3 to 555 ng m-3 across the study locations. Joint effects were identified for 9 of the 13 groups of PAs with positive associations with QTC interval. Independent effect analysis also identified and validated tris(2-chloroisopropyl) phosphate, di-n-butyl/diisobutyl adipate, and 3,5-di-tert-butyl-4-hydroxybenzaldehyde as the key exposure markers for QTC interval prolongation and changes of selected cardiovascular biomarkers. Our findings highlight the important contributions of airborne industrial chemicals to the risks of cardiovascular diseases and underline the critical need for further research on the underlying mechanisms, toxic modes of action, and human exposure risks.

Spatio-temporal repolarization dispersion before and after exercise in patients with long QT syndrome type 1 vs controls - probing into the arrhythmia substrate.

Congenital long QT syndrome (LQTS) carries an increased risk for syncope and sudden death. QT prolongation promotes ventricular extrasystoles which in the presence of an arrhythmia substrate might trigger ventricular tachycardia degenerating into fibrillation. Increased electrical heterogeneity (dispersion) is the suggested arrhythmia substrate in LQTS. In the most common subtype LQT1, physical exercise predisposes for arrhythmia and spatio-temporal dispersion was therefore studied in this context. Thirty-seven patients (57% on beta-blockers) and 37 healthy controls (mean age 31 vs 35, range 6-68 vs 6-72 years) performed an exercise test. Frank vectorcardiography was used to assess spatio-temporal dispersion as Tamplitude, Tarea, the ventricular gradient (VG), and the Tpeak-end interval from 10s-signal averages before and 7±2 min after exercise; during exercise too much signal disturbance excluded analysis. Baseline and maximum heart rates as well as estimated exercise intensity were similar, but heart rate recovery was slower in patients. At baseline QT and heart rate corrected QT (QTcB) were significantly longer in patients (as expected), while dispersion parameters were numerically larger in controls. After exercise QTpeakcB and Tpeak-endcB increased significantly more in patients (18±23 vs 7±10ms and 12±17 vs 2±6ms; p<0.001 and p<0.01). There was, however, no difference in the change in Tamplitude,Tarea and VG between groups. In conclusion, while temporal dispersion of repolarization increased significantly more after exercise in LQT1 patients, there were no signs of exercise-induced increase in global dispersion of action potential duration and morphology. The arrhythmia substrate/mechanism in LQT1 warrants further study.

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.

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.

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.

Feasibility of using KardiaMobile-L6 for QT interval monitoring during the early phase of the COVID-19 pandemic in critical care patients

The electrocardiogram (ECG) represents an essential tool to determine cardiac electrical abnormalities in COVID-19 patients, the effects of anti-SARS-CoV-2 drugs, and potential drug interactions. Smartphone-based heart monitors have increased the spectrum of ECG monitoring however, we are not aware of its reliability in critically ill COVID-19 patients. We aim to evaluate the feasibility and reliability of nurse-performed smartphone electrocardiography for QT interval monitoring in critically ill COVID-19 patients using KardiaMobile-6L compared with the standard 12-lead ECG. An observational comparative study was conducted comparing consecutive KardiaMobile-6L and 12-lead ECG recordings obtained from 20 patients admitted to the intensive care unit with SARS-CoV-2 infection and on invasive mechanical ventilation. The heart rate-corrected QT (QTc) intervals measured by KardiaMobile-6L and 12-lead ECG were compared. In 60 percent of the recordings, QTc intervals measured by KardiaMobile-6L matched those by 12-lead ECG. The QTc intervals measured by KardiaMobile-6 and 12-lead ECG were 428 ± 45 ms and 425 ± 35 ms (p = 0.82), respectively. The former demonstrated good agreement (bias = 2.9 ms; standard deviation of bias = 29.6 ms) with the latter, using the Bland–Altman method of measurement agreement. In all but one recording, KardiaMobile-6L demonstrated QTc prolongation. QTc interval monitoring with KardiaMobile-6L in critically ill COVID-19 patients was feasible and demonstrated reliability comparable to the standard 12-lead ECG.

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.

Environmental pollutant pre- and polyfluoroalkyl substances are associated with electrocardiogram parameters disorder in adults

Environmental pollutants exposure might disrupt cardiac function, but evidence about the associations of per- and polyfluoroalkyl substances (PFASs) exposure and cardiac conduction system remains sparse. To explore the associations between serum PFASs exposure and electrocardiogram (ECG) parameters changes in adults, we recruited 1229 participants (mean age: 55.1 years) from communities of Guangzhou, China. 13 serum PFASs with detection rate > 85% were analyzed finally. We selected 6 ECG parameters [heart rate (HR), PR interval, QRS duration, Bazett heart rate-corrected QT interval (QTc), QRS electric axis and RV5 + SV1 voltage] as outcomes. Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) model were conducted to explore the associations of individual and joint PFASs exposure and ECG parameters changes, respectively. We detected significant associations of PFASs exposure with decreased HR, QRS duration, but with increased PR interval. For example, at the 95th percentile of 6:2 Cl-PFESA, HR and QRS duration were − 6.98 [95% confidence interval (CI): − 9.07, − 4.90] and − 6.54(95% CI: −9.05, −4.03) lower, but PR interval was 7.35 (95% CI: 3.52, 11.17) longer than those at the 25th percentile. Similarly, significant joint associations were observed in HR, PR interval and QRS duration when analyzed by BKMR model.

Thoracic epidural analgesia prolongs postoperative QT interval on electrocardiogram in major non-cardiac surgery: a randomized comparison and a prospective cohort analysis.

Introduction: Prolongation of QT interval on electrocardiogram can be associated with perioperative lethal arrhythmia. Epidural analgesia is a commonly used modality to relieve surgical pain by blocking sensory nerves, which also blocks the autonomic nervous system and can affect QT interval. Since patient monitoring becomes much less frequent after surgery than intraoperative period, we investigated the effects of epidural analgesia on postoperative QT interval with a randomized clinical trial and a prospective cohort study. Methods: In a randomized study, we assigned 60 patients undergoing thoracic epidural analgesia to an epidural analgesia or no-epidural analgesia group, in which 3ml/h of 0.25% epidural levobupivacaine (7.5mg/h) was administered only in the epidural analgesia group during surgery. The primary outcome was the postoperative heart rate-corrected QT interval. In a prospective cohort study, patients were assigned to receive 5ml/h epidural levobupivacaine (12.5mg/h). The plasma concentration of levobupivacaine was measured using liquid chromatography-mass spectrometry. Results: The median postoperative corrected QT interval interval with 3ml/h epidural levobupivacaine was significantly longer than that without epidural analgesia. Using multiple regression analysis for the factors known to affect postoperative corrected QT interval interval, epidural analgesia was found to be an independent variable for prolongation, and the mean difference of the corrected QT interval interval with or without epidural analgesia was 23ms after adjustment. The median plasma concentration of levobupivacaine at the end of surgery was 164ng/ml with 3ml/h epidural levobupivacaine, and the correlation coefficient to the postoperative corrected QT interval interval was 0.14, showing a not significant correlation. A prospective cohort study showed that 5ml/h epidural levobupivacaine significantly prolonged postoperative corrected QT interval interval compared to preoperative baseline. The median plasma concentration of levobupivacaine was 166ng/ml with 5ml/h, the correlation coefficient of which showed no significant correlation. Conclusion: Thoracic epidural analgesia could enhance postoperative corrected QT interval prolongation after general anesthesia. The mechanism is possibly caused by blocking neighboring or part of the cardiac sympathetic nerves, rather than by systemic effects of epidurally administered levobupivacaine. Clinical trial number: UMIN000013347 for the randomized study and UMIN000041518 for the prospective cohort study, which were registered at University hospital Medical Information Network Center.