Corrected QT Research Articles

Optimal QT Correction Formula for Older Chinese: Guangzhou Biobank Cohort Study

Introduction: To identify the optimal QT correction formula for generating corrected QT (QTc) and cutoffs for prolonged QTc, and examine the associations with mortality and cardiovascular disease (CVD) in older Chinese. Methods: A prospective study included 24,611 Chinese aged 50+ years and without CVD at 2003–2008 from Guangzhou Biobank Cohort Study. QT interval was corrected by Bazett, Fridericia, Framingham and Hodges formulas. The slope and R2 of the QTc and heart rate regression were used to determine the optimal correction formula. The 95th percentile of QTc was used to defined prolonged QTc. Cox regression was used to examine associations of prolonged QTc with mortality and CVD. The net reclassification index was calculated to assess risk reclassification. Results: During an average follow-up of 15.3 years, 5,261 deaths and 5,539 CVD occurred. Optimal heart correction was observed for the Hodges formula, and Bazett formula performed the worst. Prolonged QTc corrected by Fridericia, Framingham and Hodges formulas had similar association strength with all-cause mortality, CVD mortality and incident CVD (especially coronary heart disease, myocardial infarction and ischemic stroke), with hazard ratios approximately being 1.25, 1.40, and 1.15, respectively. They also improved risk reclassification for all-cause mortality, CVD mortality and incident CVD by approximately 5%, 10%, and 6%, respectively. However, prolonged QTc corrected by Bazett formula was not associated with incident CVD and did not improve risk reclassification. Conclusions: Hodges formula outperformed other formulas for heart rate correction. Fridericia, Framingham, and Hodges formulas can be used for death and cardiovascular risk prediction.

Alleviation of oxidized lipid-induced oxidative stress and hypertension by estrogen and selected antihyperlipidemic drugs in post-menopausal Wistar rats

Lipid peroxidation is implicated in the development of hypertension and coronary artery disease, and its deleterious impact is exacerbated by estrogen (ETD) depletion in post-menopausal women. We hypothesize that treatment with ETD and antihyperlipidemic drugs, either alone or in combination, can alleviate the development of cardiovascular disease. In this study, female Wistar rats were divided into 10 groups (n = 6): Group 1 (control) underwent a Sham operation and was fed standard rat chow, whereas the other nine groups were ovariectomized (OVX) and received a diet containing either thermoxidized palm oil (TPO) or thermoxidized soya oil (TSO) for 12 weeks. ETD at 0.2 mg/kg/day, atorvastatin (ATV) at 10 mg/kg/day, and a combination of ezetimibe (EZE) and ATV (EZE at 3 mg/kg/day + ATV at 10 mg/kg/day) were administered for 12 weeks in both TSO and TPO diet groups. Blood pressure and electrocardiogram (ECG) parameters were assessed, along with serum lipid profile, atherogenic indices, and markers of oxidative stress. Both TPO and TSO diets significantly altered blood pressure and ECG parameters in OVX rats. Treatment with ATV, EZE+ATV, and ETD significantly reduced blood pressure parameters compared to the OVX+TPO group. Antihyperlipidemic drugs significantly decreased heart rate, QT interval, QRS duration, and QT corrected (QTc), whereas ETD similarly shortened the QRS and QTc duration. ATV and ETD also reduced total cholesterol, triglycerides, and very low-density lipoprotein levels, while boosting high-density lipoprotein concentrations compared to untreated OVX+TSO rats. This study demonstrates that thermoxidized oil has a deleterious effect on OVX rats by altering blood pressure, ECG parameters, and atherogenic indices. Treatment with antihyperlipidemic drugs and ETD normalized blood pressure and ECG parameters, reversed hyperlipidemia, and restored antioxidant system balance.

The usefulness of QT interval measurement as a screening tool for cascade testing in asymptomatic patients at risk of long QT syndrome

Abstract Background Long QT syndrome (LQTS), an inherited arrhythmic syndrome, remains a public health concern with up to 3000 unexpected deaths in the US annually. A simple 12-lead ECG is the most easily accessible tool for initial screening. Purpose To describe the diagnostic utility of the standard QT correction techniques in 12-Lead ECGs, in a screening population of first-degree relatives of persons with LQTS of known genotype. Methods In this single centre study, data were included on consecutive patients undergoing cascade clinical and genetic testing for LQTS, who had a first degree relative with genotype-positive LQTS, from the years 2019 to 2022. Patient demographics, baseline ECG and genetic results were obtained. The QT interval was manually calculated between three independent readers using the tangent method and corrected using the 4 most commonly used formulae: Bazett (BQTc), Fridericia (FreQTc), Framingham (FraQTc) and Hodges (HQTc). The Mean QT was calculated by taking the average of four consecutive QT measurements in lead II or V5. The QT dispersion (QTd), was also calculated by using the formula: QTd = QT max – QT min. Results Data was available on 97 patients from 14 families. The mean age at screening was 44 years, and 51.5% were males. Two-thirds of patients were asymptomatic (n = 74, 76.3%). Fifteen patients had syncopal events. 72.2% (n = 70) of patients had a family history of arrhythmic death. After clinical screening and genotyping, 46.4% (n = 45) patients were gene positive for either KCNQ1 (75.5%) or KCNH2 (24.5%). Patients with prior syncope were more likely to be gene positive (72.7% vs 39.2%, p = 0.005). The 12-Lead ECG derived QTc result is listed in Table 1, with all correction modalities showing a higher corrected QT in the genotype-positive group (p <0.001). The diagnostic performance of BQTc was similar to that of the newer formulae (FreQTc, FraQTc and HQTc) when correcting for heart rate within the range of 60 – 100bpm as listed in Table 2. At a cut-off value of 440ms, BQTc formula had a sensitivity of 51% and a specificity of 84% for predicting genotype pathogenicity as listed in Table 3. The QT dispersion was higher in patients with KCNH2 compared to those with KCNQ1 (122msec, SD 30.5 vs 74.2 msec, SD 30.4, p value <0.001). Patients with KCNH2 were more likely to require an ICD (83.3% vs 16.7%, p <0.001). The mean Schwartz score in gene positive patient was 2.6 compared to 1.9 (p <0.003). Conclusion Formula correction of QT interval to heart rate had good overall diagnostic performance. Both FreQT and FraQT had high AUROC across different heart rates, though there was no statistically significant difference seen between correction formulae. The ECG remains a good preliminary screening tool method for identifying patients with increased risk LQTS in this population. Larger studies are needed to power for comparisons between QT correction methods.

Circulating metabolites associate with the QT interval in individuals without prevalent cardiovascular disease

Abstract Background Patients with metabolic syndrome have a higher prevalence of heart-rate corrected QT (QTc) interval prolongation. Despite this the effect of circulating metabolites on the QTc is largely unknown and limited to small studies. Purpose To test for association of circulating metabolites with the QTc interval in the UK Biobank study. Methods Participants were identified from the UK Biobank with same day plasma metabolite profiling and electrocardiograms. All 249 metabolites measured underwent quality control and log transformation to account for rightward skew and zero values. 149 metabolites with inter-correlations >0.7 were excluded. Participants taking QTc-prolonging medication or with a history of ischaemic heart disease or heart failure up to 6 months after the visit, were excluded. Participants were allocated to a training group (N=21,610) or an independent test group (N=5,304), if samples were obtained at recruitment or at a second visit, respectively. In the training group, each metabolite was tested separately for association with the QTc in linear regression analyses, adjusted for clinical covariates (age, sex, fasting time, body mass index (BMI), systolic blood pressure (SBP), smoking status, diabetes, lipid-lowering drug use and dietary factors). Significant metabolites (P<5x10-4) underwent validation in the test group. Sex-stratified analyses were also performed. In the training group, variables in two models underwent regularisation by LASSO regression (10-fold cross-validation) to reduce multicollinearity and downweigh less important variables; 1) clinical variables, 2) clinical variables and validated metabolites. Coefficients were used for QTc prediction in the test group. Significance between the models was evaluated by fisher’s transformation of R-squared statistics. Results In the per metabolite multivariate analysis, 56 metabolites were associated with the QTc interval. 19 metabolites validated in the test group. For 14 of these, absolute effect sizes were >5ms when comparing individuals in the top decile of the metabolite distribution verses the bottom (Figure 1), including the ketone body 3-hydroxybutyrate (9ms), and omega-6 fatty acid to total fatty acid ratio (7.2ms). For associations in males and females separately, significant effect size differences (P<0.05) were observed for 9 metabolites (Figure 2). In the training group, the combined LASSO model selected 17 (of 19) metabolites along with age, sex, SBP and BMI. In the test group, this model R-squared was 0.115 compared with 0.081 for clinical covariates alone, representing a significant 41.9% increase in QTc variation explained (P=0.002). Conclusions This study demonstrates clinically relevant metabolite associations with the QTc in individuals without cardiovascular disease and explain a significant proportion of QTc variation. Further investigation is warranted to test for direct effects on cardiac electrophysiology and proarrhythmic potential.Validated metabolitesSignificant sex differences

Efficacy and safety of second‑generation FLT3 inhibitors in acute myeloid leukemia: A systematic review and meta‑analysis of randomized controlled trials.

Acute myeloid leukemia (AML) is one of the most frequent forms of acute leukemia and the second most common leukemia subtype in adults. In 2020, the incidence of AML in the United States was estimated to be ~4 cases per 100,000 adults. The FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutation are major prognostic indicators of AML. They are more frequently observed in younger AML patients (aged <60 years), likely due to their association with de novo. Additionally, these mutations have a stronger negative impact on survival in younger patients. Therefore, quizartinib and gilteritinib are second-generation FLT3 inhibitors that are frequently applied for treating patients with AML. However, to the best of our knowledge, few studies have compared the efficacy of second-generation FLT3 inhibitors for AML treatment. Therefore, the present study conducted a comprehensive search for studies on the efficacy and safety of FLT3 inhibitors across PubMed, Embase, the Cochrane Library and ClinicalTrials.gov. The search criteria were limited to randomized controlled trials (RCTs). Subsequently, a meta-analysis was performed on a total of five randomized controlled trials, involving 1,543 participants in total, using a random-effects model. In each RCT, compared to the salvage chemotherapy used in the control group, the groups that received second-generation FLT3 inhibitors experienced significant improvements in overall survival (hazard ratio, 0.717; 95% CI, 0.604-0.850; P<0.001). In addition, overall survival was found to be consistent across the different types of second-generation FLT3 inhibitors used and different types of AML. The risks associated with a prolonged heart-rate corrected QT interval (QTc) interval were next evaluated. Compared with the salvage chemotherapy used in the control group, the second-generation FLT3 inhibitor group exhibited a significantly higher risk of having a prolonged QTc interval (odds ratio, 6.311; 95% CI, 3.061-13.013; P<0.001). In conclusion, these findings suggest that second-generation FLT3 inhibitors can improve the overall survival of patients with AML. However, QTc prolongation is a potential adverse effect that should be monitored.

The Impact of QT-Prolonging Medications and Drug-Drug Interactions on QTc Interval Prolongation in Hospitalized Patients: A Case-Crossover Study.

Researchers have studied potential corrected QT interval (QTc) prolongation from drug-drug interactions (DDIs), raising unresolved questions about their real-world impact. This retrospective case-crossover study investigated the effects of QT-prolonging drugs and DDIs on QTc prolongation in hospitalized patients aged 45 years and above. The cohort comprised patients who had multiple hospitalizations and developed QTc prolongation (QTc > 500 ms or an increase of >60 ms from baseline) at least 24 hours after admission between 2011 and 2019. Conditional logistic regression compared drug exposure between hospitalizations with QTc prolongation (case window) and those without (reference window). Among 2,276 patients (mean age 71; 43.8% female), the use of QT-prolonging drugs significantly increased the risk of QTc prolongation (odds ratio: 2.42 (95% confidence interval: 1.95-3.02)). The risk was higher with drugs of "known risks" (OR: 3.78 (2.91-4.90)) and "conditional risk" (OR: 2.08 (1.65-2.62)). DDIs, particularly involving multiple "known risk" drugs (OR: 7.86 (4.96-12.45)), strong cytochrome P450 enzyme inhibitors (OR: 5.57 (2.75-11.30)), or the concurrent use of ≥4 QT-prolonging drugs with any risk (OR: 5.28 (3.96-7.03)) substantially increased the risk. Cautious prescribing for patients with multiple risk factors is important to minimize the likelihood of QTc prolongation. However, when considering enhanced monitoring or drug choices, it is crucial to carefully evaluate the overall risk of QT prolongation against the benefits of treatment to ensure optimal patient care.

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.

Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer

Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase I multicenter study of BMS-986365 in patients with progressive mCRPC. Patients who progressed on androgen deprivation therapy, one or more ARPIs, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (part A) and expansion (part B) of BMS-986365 up to 900 mg twice daily. Primary objectives were safety and tolerability, and to define maximum tolerated dose and/or recommended phase II dose. Key secondary endpoints included decline in prostate-specific antigen ≥50% (PSA50) and radiographic progression-free survival (rPFS). Parts A and B enrolled 27 and 68 patients, respectively. In part B, the median number of prior therapies was 4 (range 2-11). The most common treatment-related adverse events were asymptomatic prolonged corrected QT interval (47%) and bradycardia (34%). Part A maximum tolerated dose was not reached and recommended phase II dose selection is ongoing. Across part B three highest doses (400-900 mg twice daily, n= 60), PSA50 was 32% (n= 19), including 50% (n= 10/20) at 900 mg; median rPFS (95% confidence interval) was 6.3 months (5.3-12.6 months), including 8.3 months (3.8-16.6 months) at 900 mg; and rPFS was longer in patients without versus with prior chemotherapy: 16.5 months (5.5 months-not evaluable) versus 5.5 months (2.7-8.3 months), respectively. Efficacy was observed in patients with mCRPC with AR ligand binding domain (LBD) WT or with AR LBD mutations. BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with mCRPC with potentially higher benefit in chemotherapy-naive patients. These data show the potential of BMS-986365 to overcome resistance to current ARPIs, regardless of AR LBD mutation status.

Relevance of accurate QT correction in the assessment of long QT syndrome

BackgroundLong QT syndrome (LQTS) is a genetic cardiac disease, where the corrected QT (QTc) interval is prolonged. It can cause arrhythmias and lead to a sudden cardiac death. Duration of the QT interval depends on the heart rate and this dependency is treated with QT correction. However, the current QT correction methods have well known problems and limitations. ObjectiveWe study the relevance of QT correction method in evaluating the risk of LQTS. We evaluate the reliability of the present and recently developed QT correction methods to discriminate LQTS subjects from healthy controls. MethodsWe use the clinically prevalent QT correction methods, particularly Bazett and Fridericia, in comparison with the recently developed AccuQT method. The data of healthy controls and LQTS subjects is extracted from the Rochester THEW database. The analysis accounts for sex, major LQTS subtypes, and beta-blocker treatment. ResultsQT values corrected with AccuQT discriminate the healthy and LQTS samples with the best accuracy, leading to (TP, TN) = (0.87, 0.65) with the conventional 450 ms threshold for LQTS. Fridericia correction yields lower sensitivity (0.71), but comparable balanced accuracy, whereas Bazett shows significantly less accurate results due to overcorrection at lower heart rates. ConclusionThe selected QT correction method is important in the identification of LQTS. In particular, the use of Bazett correction should be questioned. Fridericia correction yields good results with respect to its simplicity. AccuQT has the best accuracy out of all the methods for LQTS discrimination. For practical applicability, however, AccuQT needs further validation in realistic clinical conditions.

Is the development of arrhythmia predictable in rheumatoid arthritis?

This study aimed to determine whether there is a difference in the electrocardiography (ECG) measurements of healthy controls and rheumatoid arthritis (RA) patients and to predict whether they can be used to determine the risk of arrhythmia in patients. The prospective study included 50 cardiac asymptomatic RA patients (38 males, 12 females; mean age: 46.8±9.1 years; range, 18 to 60 years) who met the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology RA criteria and 50 healthy volunteers (34 males, 16 females; mean age: 43.4±10.4 years; range, 18 to 60 years) as a control group between June 1, 2022, and August 31, 2022. Disease activity of the patients was calculated with the Disase Activity Score (DAS28). Heart rate, minimum and maximum QT intervals, QT dispersion, minimum and maximum P waves, P wave dispersion (Pd), minimum and maximum Tp-e intervals, Tp-e dispersion, minimum and maximum corrected QT (QTc) intervals, QTc dispersion, and the Tp-e/QTc ratio in ECGs were calculated. The mean disease duration of the RA group was 9.09±5.74 years. The mean C-reactive protein level was 9.83±8.29, the mean erythrocyte sedimentation rate was 26.12±16.28 mm/h, and the mean DAS28 was 3.03±0.37. There was a statistically significant increase in the maximum P wave, Pd, maximum QT, QT dispersion, maximum QTc, QTc dispersion, maximum Tp-e, Tp-e dispersion, and Tp-e/QTc dispersion parameters in the RA group compared to the control group, while there was a significant decrease in the minimum P wave, minimum QT, and minimum QTc parameters. In our study, the Pd, QTc dispersion, Tp-e dispersion, and Tp-e/QTc dispersion values of our patients, which indicate the risk of atrial and ventricular arrhythmia, were found to be significantly higher. This finding suggests that our patients had an increased risk of cardiac morbidity and mortality. Arrhythmias are the likely source of the increase in sudden cardiac death in RA, and these new indicators measured on ECG can be used as standardized cardiovascular morbidity and mortality indicators in the future.

Prevalence, Outcomes, and Predictors of Prolonged Corrected QT Interval in Hydroxychloroquine-Naïve Hospitalized COVID-19 Patients.

The studies regarding prevalence, outcomes, and predictors of prolonged corrected QT (QTc) among COVID-19 patients not on QTc-prolonging medication are not available in the literature. In this retrospective cohort study, the QTc of 295 hospital-admitted COVID-19 patients was analyzed and its association with in-hospital mortality was determined. The QTc was prolonged in 14.6% (43/295) of the study population. Prolonged QTc was seen in patients with older age (P = 0.018), coronary artery disease (P = 0.001), congestive heart failure (P = 0.042), elevated N-terminal-pro-B-type natriuretic peptide (NT-ProBNP) (P < 0.0001), and on remdesivir (P = 0.046). No episode of torsades de pointes arrhythmia or any arrhythmic death was observed among patients with prolonged QTc. The mortality was significantly high in patients with prolonged QTc (P = 0.003). The multivariate logistic regression analysis showed coronary artery disease (odds ratio (OR): 4.153, 95% CI 1.37-14.86;P = 0.013), and NT-ProBNP (ng/L) (OR: 1.000, 95% CI 1.000-1.000;P = 0.007) as predictors of prolonged QTc. The prolonged QTc was associated with the worst in-hospital survival (p by log-rank 0.001). A significant independent association was observed between prolonged QTc and in-hospital mortality in multivariate cox-regression analysis (adjusted hazard ratio: 3.861; (95% CI 1.719-6.523), P < 0.0001). QTc was found to be a marker of underlying comorbidities among COVID-19 patients. Prolonged QTc in hospitalized COVID-19 patients was independently associated with in-hospital mortality.

Thorough QT/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults.

Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia's QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.

Prognostic Value and Limits of Heart Rate and QT—Corrected in A Large Population

Background: The study aimed to compare the prognostic importance of the heart rate (HR) and QT—corrected (QTc) according to Fridericia, Framingham, and Bazett with respect to all-cause mortality in a large non-selected population. Methods: The analysis of digital electrocardiograms archived from 2008 to 2022 in the metropolitan area of Modena, Italy, was carried out. The population under study was divided into three groups based on age, and survival analysis was performed. Results: 131,627 patients were enrolled and, during the follow-up (mean 1641.4 days), all-cause mortality was 8.9%. Both HR and QTc were associated with mortality. All-cause mortality significantly increased with HR values greater than 81 BPM and QTc values greater than 440 msec in young subjects and 455 msec in old subjects (values of the 75th percentiles/optimal operating point). A Cox analysis confirmed the better prognostic value of Bazett’s QTc and HR in the whole population and in the three age-groups. Conclusion: Bazett’s method performed better than the others, but, unexpectedly, the HR had the same or an even better correlation with all-cause mortality. Since the HR is simple and readily available, its evaluation should be improved. However, QTC and HR values are difficult to define, causing many confounding factors, and further population studies are required.

Compatibility study of topical 0.25% hypericin (HyBryteTM) application in subjects with mycosis fungoides: Results of the HPN‐CTCL‐02 study

AbstractBackgroundHyBryteTM is a photodynamic therapy of topical hypericin that has recently been shown to be safe and efficacious in early stage cutaneous T‐cell lymphoma (CTCL). However, its efficacy, absorption, and effect on heart function parameters in patients who require greater HyBryteTM exposure is unknown.ObjectivesThe primary objectives in this study were to assess hypericin blood levels using a validated detection method with a cut‐off value of 0.05 ng/mL and to determine if topical HyBryteTM induces any electrocardiogram (EKG) changes during 8 weeks of treatment. A secondary endpoint of this study was to assess the effectiveness of HyBryteTM in this patient population as well as assessing a different additional light device than the one used in the Phase 3 HPN‐CTCL‐01/fluorescent light activated synthetic hypericin trial also entitled “A phase 3 multicenter randomised placebo‐controlled study to determine the efficacy of topical hypericin and light irradiation for the treatment of cutaneous T‐cell lymphoma”.MethodsA confirmatory, prospective, open‐label, single‐centre, interventional study focused on stage IB and IIA mycosis fungoides with more than 10% of their body surface areas involved was performed.ResultsHypericin concentration in K2EDTA whole blood samples collected before and after light activation at Weeks 4, 6 and 8 showed an average blood concentration of 0.13 ng/mL and achieved steady state by Week 4. EKGs were examined for clinical changes at each study visit, including changes in QT intervals and correction of heart rates. No significant clinical changes in EKGs were observed.ConclusionsHypericin does not appear to be significantly absorbed through the skin nor cause significant cardiac changes overall or prolong the QT interval when applied topically. A larger study is necessary to clearly define these results.

Deep Learning–Augmented ECG Analysis for Screening and Genotype Prediction of Congenital Long QT Syndrome

Congenital long QT syndrome (LQTS) is associated with syncope, ventricular arrhythmias, and sudden death. Half of patients with LQTS have a normal or borderline-normal QT interval despite LQTS often being detected by QT prolongation on resting electrocardiography (ECG). To develop a deep learning-based neural network for identification of LQTS and differentiation of genotypes (LQTS1 and LQTS2) using 12-lead ECG. This diagnostic accuracy study used ECGs from patients with suspected inherited arrhythmia enrolled in the Hearts in Rhythm Organization Registry (HiRO) from August 2012 to December 2021. The internal dataset was derived at 2 sites and an external validation dataset at 4 sites within the HiRO Registry; an additional cross-sectional validation dataset was from the Montreal Heart Institute. The cohort with LQTS included probands and relatives with pathogenic or likely pathogenic variants in KCNQ1 or KCNH2 genes with normal or prolonged corrected QT (QTc) intervals. Convolutional neural network (CNN) discrimination between LQTS1, LQTS2, and negative genetic test results. The main outcomes were area under the curve (AUC), F1 scores, and sensitivity for detecting LQTS and differentiating genotypes using a CNN method compared with QTc-based detection. A total of 4521 ECGs from 990 patients (mean [SD] age, 42 [18] years; 589 [59.5%] female) were analyzed. External validation within the national registry (101 patients) demonstrated the CNN's high diagnostic capacity for LQTS detection (AUC, 0.93; 95% CI, 0.89-0.96) and genotype differentiation (AUC, 0.91; 95% CI, 0.86-0.96). This surpassed expert-measured QTc intervals in detecting LQTS (F1 score, 0.84 [95% CI, 0.78-0.90] vs 0.22 [95% CI, 0.13-0.31]; sensitivity, 0.90 [95% CI, 0.86-0.94] vs 0.36 [95% CI, 0.23-0.47]), including in patients with normal or borderline QTc intervals (F1 score, 0.70 [95% CI, 0.40-1.00]; sensitivity, 0.78 [95% CI, 0.53-0.95]). In further validation in a cross-sectional cohort (406 patients) of high-risk patients and genotype-negative controls, the CNN detected LQTS with an AUC of 0.81 (95% CI, 0.80-0.85), which was better than QTc interval-based detection (AUC, 0.74; 95% CI, 0.69-0.78). The deep learning model improved detection of congenital LQTS from resting ECGs and allowed for differentiation between the 2 most common genetic subtypes. Broader validation over an unselected general population may support application of this model to patients with suspected LQTS.

Electrocardiographic abnormalities in patients with sickle cell disease: A systematic review and meta-analysis.

Previous studies have documented that electrocardiography (ECG) can reveal a range of abnormalities, offering valuable insights into the cardiac evaluation of patients with sickle cell disease (SCD). The objective of this study is to assess the patterns of ECG abnormalities observed in these patients with SCD, and to determine their prevalence. We systematically reviewed the literature using online databases of PubMed, Scopus, Web of Science, Embase, and Google Scholar to identify original studies that reported findings of standard ECG assessments in patients with SCD. Statistical analyses were performed using the random effects model. Additional analyses including sensitivity analysis and subgroup analysis were also conducted. Analysis of data from 59 studies involving 897,920 individuals with SCD revealed that 75% of these patients had abnormal ECG findings (67%-81%), which were predominantly nonspecific ST-T changes, left ventricular hypertrophy, T-wave changes, prolonged corrected QT (QTc) interval, and ischemic changes. Besides, it was shown that these patients had significantly higher odds of having any ECG abnormalities (OR of 17.50, 4.68-65.49), right atrial enlargement (6.09, 1.48-25.09), left ventricular hypertrophy (3.45, 1.73-6.89), right ventricular hypertrophy (7.18, 2.28-22.57), biventricular hypertrophy (10.11, 1.99-51.38), prolonged QTc interval (5.54, 2.44-12.59), ST depression (3.34, 1.87-5.97), and T-wave changes (5.41, 1.43-20.56). Moreover, the mean of QTc interval was significantly higher among those with SCD (23.51milliseconds, 16.08-30.94). Our meta-analysis showed a higher prevalence of abnormal ECG findings among individuals with SCD. A significant proportion of these patients had various ECG abnormalities, suggesting a potential need for regular ECG assessments for patients with SCD.

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.

Prevalence of prolonged QTc interval among HIV infected patients on highly active antiretroviral therapy (HAART) and its relationship with CD4 cells count and viral load at a tertiary hospital in North Eastern Nigeria.

Patients living with HIV infection remain at increased risk of cardiovascular diseases and sudden cardiac death. Various prevalence of electrocardiographic (ECG) abnormalities among HIV-infected patients were reported: Attamah et al reported the prevalence of electrocardiographic abnormalities among HIV-infected patients as 34.5%, while Orunta et al reported a prevalence of 42.9%, and Njoku et al reported a prevalence of 93.0%. Human immunodeficiency virus-infected patients are at increased risk of developing prolonged QT interval. Sani et al reported the prevalence of prolonged corrected QT interval among HIV-infected patients as 45.0%. Innocent et al reported a prevalence of48.0%, while Ajala et al reported a prevalence of 18%. Prolonged QTc interval increases the risk of premature ventricular contraction which can degenerate into ventricular tachycardia and or ventricular that can result in sudden cardiac death. The study was a cross-sectional conducted among HIV-infected patients receiving HAART at the Federal Medical Centre Nguru, Yobe State, North Eastern Nigeria. One hundred and seven (107) subjects were recruited into the study comprising thirty-three (37.0%) males and 70(65.4%) females. The mean CD4 cell count, and viral load of the studied patients were 612.64±34.75 cells/μL and4646.30±58.68 copies/mL respectively. Twenty (18.7%) patients had prolonged QTc interval, this gave us the prevalence of prolonged QTc in this study as 18.7%. The commonest cardiac rhythm was sinus rhythm (69.2%), followed by sinus tachycardia (26.2%) and atrial fibrillation 5(4.7%). Other electrocardiographic findings include First-degree atrioventricular block was seen in seven (6.5%) patients, Premature ventricular contractions were found in16.8%, RBBB was observed in 2.8%, 3.7% of patients had LBBB and 4.7% had left posterior hemiblock. The distribution of QTc interval according to CD4 cells count and viral revealed a statistically significant difference across the groups. All the patients with prolonged QTc interval had lower CD4 cells count and higher viral load suggesting that HIV disease severity is associated with prolonged QTc interval. In conclusion, the study revealed that the prevalence of prolonged QTc interval among HIV infected patients on highly active antiretroviral therapy was found to be 18.7%, and that HIV disease severity increases the risk of developing prolonged QTc interval.

Corrected QT Interval and Outcomes of Dialysis Patients with Symptomatic Peripheral Artery Disease: A Prospective Cohort Study

Background: Peripheral artery disease (PAD) is common and associated with a higher risk of cardiovascular morbidity and mortality in dialysis patients. A longer corrected QT (QTc) interval has been associated with adverse cardiovascular events and mortality in the general population and patients with end-stage kidney disease. However, little evidence is available on the predictive value of QTc in dialysis patients with PAD. Methods: We conducted a prospective cohort study of 356 dialysis patients with symptomatic PAD undergoing endovascular therapy. We performed the resting 12-lead electrocardiogram (ECG) at baseline. Cox regression analyses were used to assess the association of QTc with all-cause mortality and major adverse cardiovascular events (MACEs), defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Results: The mean age was 67.3 ± 11.5 years; 41.6% of participants were women. The median QTc was 471 (interquartile ranges 448–491) milliseconds (ms). During a median follow-up of 2.2 years, 188 (52.8%) patients died, and MACEs occurred in 119 (33.4%) patients. In multivariable-adjusted models, patients in tertile 3 of QTc levels had a significantly greater risk of all-cause mortality (hazard ratio [HR] 2.41, 95% confidence intervals [CI] 1.58–3.69) and MACEs (HR 1.90, 95% CI 1.15–3.13) than those in tertile 1. Similarly, each 10-ms increase in the baseline QTc predicted a higher risk of all-cause death (HR 1.15, 95% CI 1.09–1.21) and MACEs (HR 1.15, 95% CI 1.07–1.23). Conclusions: QTc prolongation was independently associated with adverse outcomes among dialysis patients with symptomatic PAD.

Comparison of QT Correction Methods in the Pediatric Population of a Community Hospital: A Retrospective Study

Comparison of QT Correction Methods in the Pediatric Population of a Community Hospital: A Retrospective Study