Baseline QTc Research Articles

DETECTION OF CONGENITAL LONG QT SYNDROME WITH ARTIFICIAL INTELLIGENCE

DETECTION OF CONGENITAL LONG QT SYNDROME WITH ARTIFICIAL INTELLIGENCE

Increasing Daily Physical Activity and Its Effects on QTc Time in Severe to Very Severe COPD: A Secondary Analysis of a Randomised Controlled Trial

Approximately, half of COPD patients die from cardiovascular diseases. A prolongation of cardiac repolarization (measured as QTc interval) is associated with cardiovascular events or cardiovascular deaths in populations of older adults and COPD. One way to reduce the QTc could be to increase physical activity (PA). We investigated whether QTc can be reduced by an increase in PA in patients with severe COPD. This is a secondary outcome analysis from a randomized controlled trial investigating the effects of a 3 months pedometer based program to improve PA. 12-lead ECG was assessed at baseline and after 3 months. We measured PA using a validated triaxial accelerometer. Data were analyzed from 59 participants. Multiple regression modeling, including adjustment for baseline QTc, sex, QT prolonging medications, BMI, smoking status and FEV1%, showed no evidence for an association between an improvement of ≥15% PA and QTc reduction. A 15% improvement in PA according to step counts over 3 months seems not to reduce QTc interval by its MCID of 20 ms in patients with severe to very severe COPD.

Impact of age and sex on hyperoxia-induced cardiovascular pathophysiology

Hyperoxia is characterized by pronounced inflammatory responses, pulmonary cell apoptosis, and adverse cardiac remodeling due to an excess supply of oxygen. Hyperoxic episodes are frequent in mechanically ventilated patients and are associated with in-hospital mortality. This study extends the analysis of prior published research by our group as it investigates the influence of age in male and female rodents exposed to hyperoxic conditions. Age is an independent cardiovascular risk factor, often compounded by variables like obesity, diabetes, and a decline in sex hormones and their receptors. This study simulates clinical hyperoxia by subjecting rodents to > 90 % of oxygen for 72 h and compares the changes in cardiac structural and functional parameters with those exposed to normal air. While in both sexes conduction abnormalities with ageing were discernible, aged females owing to their inherent higher baseline QTc, were at a higher risk of developing arrhythmias as compared to age-matched males. Quantitative real-time RT-PCR and western blot analysis reflected altered expression of cardiac potassium channels, resulting in conduction abnormalities in aged female rodents. Unaffected by age and sex, hyperoxia-treated mice had altered body composition, as evidenced by a considerable reduction in body weight. Interestingly, compensatory hypertrophy observed as a protective mechanism in young males was absent in aged males, whereas protection of hearts from hyperoxia-induced cardiac hypertrophy was absent in aged female mice, both of which may be at least in part due to a reduction in sex steroid receptors and the systemic steroid levels. Finally, statistical analysis revealed that hyperoxia had the greatest impact on most of the cardiac parameters, followed by age and then sex. This data established an imperative finding that can change the provision of care for aged individuals admitted to ICU by elucidating the impact of intrinsic aging on hyperoxia-induced cardiac remodeling.

Estimation of the QTc interval in the presence of right bundle branch block: A comparative study using validated formulae for left bundle branch block

BackgroundAdequate measurement of the QT interval is of clinical importance in order to identify patients at higher risk for ventricular arrhythmias. Previous studies have described different methods to estimate baseline QT in patients with left bundle branch block (LBBB). However, the evidence regarding the assessment of the QT in patients with right bundle branch block (RBBB) is scarce. AimTo analyze the feasibility and reliability of the different formulae described for LBBB in the estimation of the baseline QT in the presence of RBBB. MethodsWe performed an observational study including patients who underwent electrophysiology study and/or ablation. Two types of RBBB were considered: 1) pacing-induced and 2) transient true RBBB. QRS, JT and QT intervals were measured during baseline and RBBB. Estimated QTc was calculated using LBBB formulae: Bogossian, Rautaharju, Tabatabaei, Tang-Rabkin, Yankelson, Wang. Linear correlation and intraclass correlation coefficients (ICC) were used to assess the reliability of these formulae for the estimation of baseline QTc. ResultsWe finally included a total of 100 patients. Correlations between baseline and estimated QTc were strong (R > 0.7) for all the formulae except for Tabatabaei. Yankelson and Wang showed the highest reliability (ICC = 0.775 and 0.727, respectively). Yankelson appeared to be the most accurate formula, with a mean estimated QTc closest to baseline values. ConclusionPreviously described formulae for LBBB exhibited marked differences regarding reliability in the estimation of the QTc interval in the presence of RBBB. According to our results, Yankelson showed the most consistent and accurate agreement in this setting.

Early Alterations of QTc in Patients with COVID-19 Treated with Hydroxychloroquine or Chloroquine in Libreville, Gabon.

The objective of this study was to analyze the effect of hydroxychloroquine or chloroquine associated with azithromycin on the QTc interval in Gabonese patients treated for COVID-19. Methods: This was an observational study conducted from April to June 2020, at the Libreville University Hospital Center in Gabon. Patients admitted for COVID-19 and treated with hydroxychloroquine or chloroquine, each combined with azithromycin were included. The QTc interval was measured upon admission and 48 h after starting treatment. The primary endpoint was QTc prolongation exceeding 60 ms and/or a QTc value exceeding 500 ms at 48 h. Results: Data from 224 patients, 102 (45.5%) who received hydroxychloroquine and 122 treated with chloroquine, were analyzed. The median baseline QTc was 396 (369–419) ms. After 48 h of treatment, 50 (22.3%) patients had a significant prolongation of QTc. This tended to be more frequent in patients treated with chloroquine (n = 33; 27.0%) than in those treated with hydroxychloroquine (n = 17; 16.7%) (p = 0.06). QTc prolongation exceeding 60 ms was found in 48 (21.3%) patients, while 11 patients had a (4.9%) QTc exceeding 60 ms at admission and exceeding 500 ms after 48 h. Conclusion: Early QTc prolongation is frequent in COVID-19 patients treated with hydroxychloroquine or chloroquine in association with azithromycin.

The long-term efficacy of left cardiac sympathetic denervation in long QT syndrome

Objective: To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD) for long QT syndrome(LQTS) patients with either recurrence on drug therapy intolerance/refusal. Methods: This study was a retrospective cohort study. The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012. This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People's Hospital or Beijing Tongren Hospital. The patients were allocated into 3 groups: high-risk group(n=13, baseline QTc ≥550 ms or symptomatic in the first year of life or highly malignant genetics); intermediate-risk group(n=10, 500 ms≤baseline QTc<550 ms, symptomatic after the first year and without highly malignant genetics); low-risk group(n=5, baseline QTc<500 ms, symptomatic after the first year and without highly malignant genetics). LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery (VATS). Patients were regularly followed up until 20 years after the surgery. Data were collected before and 1 year after surgery and at the last follow-up. Patients' electrocardiograph(ECG), cardiac events and surgery-related complications were recorded. Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes. Results: A total of 28 LQTS patients, aged 20.5 (15.0, 37.5) and underwent LCSD surgery, were enrolled in this study, including 23(82.1%) women. There were 11(39.3%) patients treated with traditional approach while 17(60.7%) with VATS-LCSD. There were 19(67.9%) patients had positive genetic test results, including 4 LQT1, 12 LQT2, 1 LQT1/LQT2 mixed type, and 2 Jervell-Lange-Nielsen (JLN) syndrome. The median follow-up period was 189.3(138.7, 204.9) months. The dropout rate was 10.7%(3/28) while 3 patients in the intermediate-risk group were lost to follow-up. Horner syndrome occurred in 1 patient (in the high-risk group). Sudden cardiac deaths were observed in 3 (12.0%) patients (all in the high-risk group), and 12 patients (48.0%) had syncope recurrences (2 in low-risk group, 3 in intermediate-risk group and 7 in high-risk group). A significant reduction in the mean yearly episodes of cardiac events was observed, from (3.5±3.3) before LCSD to(0.2±0.1) at one year after LCSD and (0.5±0.8) at last follow up(P<0.001). The mean QTc was shortened from (545.7±51.2)ms before the surgery to (489.0±40.1)ms at the last follow-up (P<0.001). Among the 20 patients with basic QTc ≥500 ms and completing the follow-up, the QTc intervals of 11(55.0%) patients were shortened to below 500 ms. The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-, intermediate- and high-risk groups, and the difference was statistically significant (χ²=7.24, log-rank P=0.026). No difference was found in the event free survival rates among LQT1, LQT2 and undefined gene patients (χ²=5.20, log-rank P>0.05). Conclusions: LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up. LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy. However, high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.

AZD8233 antisense oligonucleotide targeting PCSK9 does not prolong QT interval.

AZD8233 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) antisense oligonucleotide under development for treatment of hypercholesterolaemia. A prespecified concentration-QT analysis was performed based on data from a single ascending dose study that was prospectively designed to act as a TQT study substitute. Subcutaneous single doses ranging from 4 to 120 mg were evaluated in 73 adult healthy male subjects. Time-matched 12-lead digital ECG and plasma concentrations (n = 15) were measured at baseline and up to 48 hours after dose in each subject. The analysis was performed using a linear mixed effect model, where change from baseline QTc (ΔQTc) was a dependent variable and time-matched AZD8233 concentration was an independent variable. The high clinical exposure scenario was defined as 1.7-fold the expected Cmax following an assumed therapeutic dose of 60 mg, which corresponds to AZD8233 plasma concentration of 1.39 μg/mL. Estimated placebo-corrected and baseline-adjusted QTcF interval (ΔΔQTcF) at this concentration was -2.2ms (90% CI: -4.11, -0.28). Furthermore, the upper 90% ΔΔQTcF confidence interval was estimated to be below 10ms at all observed concentrations. As the effect on ΔΔQTcF is below the threshold for regulatory concern (10ms), it can be concluded that AZD8233 does not induce QTcF prolongation at the high clinical exposure scenario.

QTc Dynamics Following Cardioversion for Persistent Atrial Fibrillation.

BackgroundCardioversion (CV) for atrial fibrillation (AF) is common. We aimed to assess changes in QTc over time following electrical CV (ECV) for persistent AF, and to compare the benefit of using continuous Holter monitoring vs. conventional follow-up by ECG.MethodsProspective observational cohort study. We comprised 90 patients admitted to our center for elective ECV due to persistent AF who were prospectively enrolled from July 2017 to August 2018. All patients underwent 7-days Holter started prior to ECV. Baseline QTc was defined as median QTc during 1 h post ECV. The primary endpoint was QTc prolongation defined as QTc ≥500 ms, or ≥10% increase (if baseline QTc was >480 ms). Conventional monitoring was defined as 2-h ECG post ECV.ResultsMean age was 67 ± 11 years and 61% were male. Median baseline QTc was 452 ms (IQ range: 431–479 ms) as compared with a maximal median QTc of 474 ms (IQ range: 433–527 ms; p <0.001 for the change in QTc from baseline). Peak median QTc occurred 44 h post ECV. The primary endpoint was met in 3 patients (3%) using conventional monitoring, compared with 39 new patients (43%) using Holter (p <0.001 for comparison). The Holter monitoring was superior to conventional monitoring in detecting clinically significant QTc prolongation (OR = 13; p <0.001).ConclusionsECV of patients with persistent AF was associated with increased transient risk of QTc prolongation in nearly half of the patients. Peak median QTc occurs during end of second day following ECV and prolonged ECG monitoring provides superior detection of significant QTc prolongation compared with conventional monitoring.

Electrocardiographic parameters and the risk of new-onset atrial fibrillation in the general population

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. This study is further supported by the Senior Scientist Grant from Dutch Heart Foundation (03-004-2021-T050). Background The (shape of the) association and sex-differences between electrocardiographic parameters and new-onset atrial fibrillation (AF) remain incompletely understood. Purpose To investigate the association between electrocardiographic parameters and new-onset atrial fibrillation among men and women in the general population. Methods 12,212 participants free of AF from a large population-based cohort study were included. Up to five repeated measurements of electrocardiographic parameters including PR, QRS, QT, QT corrected for heart rate (QTc), JT, RR interval, and heart rate were assessed at baseline and follow-up examinations. Cox proportional hazards models and joint models, both adjusted for cardiovascular risk factors, were used to determine the (shape of) association between baseline and longitudinal electrocardiographic parameters with new-onset AF. Additionally, we evaluated potential sex-differences. Results During a median follow-up of 9.3 years, 1,282 incident AF cases occurred among 12,212 participants (mean age 64.9 years, 58.2% women). Penalized cubic splines revealed that associations between baseline electrocardiographic measures and risk of new-onset AF were generally U-shaped (Figure 1). Sex-differences in terms of the shape of the various associations were most apparent for baseline PR, QT, QTc, RR, and heart rate in relation to new-onset AF. Longitudinal measures of PR (hazard ratio (HR), 95% confidence interval (CI), 1.43, 1.02-2.04, p=0.0393), and QTc interval (HR, 95% CI, 5.23, 2.18-12.45, p=0.0002) were significantly associated with new-onset AF. Sex-stratified analyses showed that the longitudinal associations were more prominent among men. Conclusions Baseline electrocardiographic measures and risk of new-onset AF were generally U-shaped. Longitudinal electrocardiographic measures of PR, and QTc interval were significantly associated with new-onset AF, more pronounced in men. Our findings imply that different thresholds of electrocardiographic parameters might translate to a differential risk of AF among men and women, and that treatment options targeting specific electrocardiographic parameters might prevent AF in the general population, in particular in men.

Hydroxychloroquine and Azithromycin Combination in the Management of COVID-19 Infection: Safety and Effectiveness Challenges.

The treatment of COVID-19 disease remains a dilemma so far because there is no approved therapy for it. This study aimed to evaluate the use of hydroxychloroquine and azithromycin combination in treatment. This study was carried out to determine the safety and effectiveness of hydroxychloroquine and azithromycin combination in COVID 19 patients. This study included 90 adult COVID 19 patients. Treatment of all patients followed Egyptian Ministry of Health COVID-19 protocols, receiving a combination of hydroxychloroquine 400mg twice on day 1, then 200 mg twice daily in addition to azithromycin 500mg/day for 5 days. ECG findings, especially the QTc interval, were assessed before and after 5 days from the administration. All patients showed a statistically significant higher post-treatment QTc readings (433.6 ± 37.2) compared to baseline QTc (402.4 ± 31.3) at p<0.005 with a median QTc prolongation by 26 mSec and IQR (17.8-41.3), but without serious clinical complications. Only 5.6% of patients showed QTc more than 500 mSec and no torsade de points or cardiac arrest. Geriatric patients were at higher risk for QTc prolongation compared to patients aged less than 65 years but without a significant difference as regards the median max QTc difference p˂0.65. The expected therapeutic effectiveness was 82.5% for moderate patients compared to 26% for severe patients (P<0.005). In a modest safety profile, we support the evidence that HQ/AZ therapy can be used to treat Covid-19 infection with more effectiveness in moderate rather than severe cases, which might be a reflection of the time of administration in the disease course.

Prevalence of ECG testing and characteristics among new hydroxychloroquine and chloroquine users within a multi-center tertiary care center.

COVID-19 raised concern regarding cardiotoxicity and QTc prolongation of hydroxychloroquine (HCQ) and chloroquine (CQ). We examined the frequency and patient factors associated with ECG testing and the detection of prolonged QTc among new HCQ/CQ users in a large academic medical system. 10,248 subjects with a first HCQ/CQ prescription (1/2015–3/2020) were included. We assessed baseline (1 year prior to and including day of initiation of HCQ/CQ through 2 months after initial HCQ/CQ prescription) and follow-up (10 months after the baseline period) patient characteristics and ECGs obtained from electronic health records. Among 8384 female HCQ/CQ new users, ECGs were obtained for 22.3%, 14.3%, and 7.6%, at baseline, follow, and both periods, respectively. Among 1864 male HCQ/CQ new users, ECGs were obtained more frequently at baseline (29.7%), follow-up (18.0%), and both periods (11.3%). Female HCQ/CQ users with a normal QTc at baseline but prolonged QTc (> 470 ms) at follow-up (13.1%) were older at HCQ/CQ initiation [mean 64.7 (SD 16.5) vs. 58.7 (SD 16.9) years, p = 0.004] and more likely to have history of myocardial infarction (41.0% vs. 21.6%, p = 0.0003) compared to those who had normal baseline and follow-up QTc. The frequency of prolonged QTc development was similar (12.4%) among male HCQ/CQ new users (> 450 ms). Prior to COVID-19, ECG testing before and after HCQ/CQ prescription was infrequent, particularly for females who are disproportionately affected by rheumatic diseases and were just as likely to develop prolonged QTc (> 1/10 new users). Prospective studies are needed to guide future management of HCQ/CQ therapy in rheumatic populations.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00296-022-05125-0.

CPNP 2022 Annual Meeting Poster Abstracts

CPNP 2022 Annual Meeting Poster Abstracts

Practical Approaches to Antipsychotic-Associated Corrected QT Interval Prolongation in Patients With Serious Mental Illness: A Review of Cases

Background: There is no consensus for assessment and management of patients with serious mental illness (SMI) who are at risk for cardiac morbidity and mortality due to antipsychotic-associated QTc prolongation. Objective: The objective of this review was to assess methods for risk scoring, QT correction calculation, and clinical management in SMI patients with antipsychotic-associated QTc prolongation. Methods: A search was performed in PubMed for case reports that described QTc prolongation in adult patients with schizophrenia or bipolar disorder prescribed an antipsychotic. Reports published in North America between 2000 and 2020 were eligible. The Mayo, Tisdale, and RISQ-PATH scoring tools were applied to cases to categorize risk level. Results: Seventeen cases were included. Most patients were prescribed a second-generation antipsychotic for schizophrenia, with baseline and maximum QTc values of 429 milliseconds and 545 milliseconds, respectively. The Mayo scoring tool identified 17 (100%) cases as “high risk,” Tisdale identified 9 (53%) cases as “moderate risk” and 7 (41%) cases as “low risk,” while RISQ-PATH identified 9 (53%) cases as “not low risk” and 8 (47%) cases as “low risk.” Three cases reported the QT correction formula utilized (18%). The most common intervention to address antipsychotic-associated QTc prolongation was switching to a different antipsychotic (35%). Approximately one third of patients experienced Torsades de Pointes. Conclusion: There is a lack of standardization for antipsychotic-associated QTc prolongation risk assessment and management in patients with SMI. This review provides real-world data representing actual clinical practice.

QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs

IntroductionMany antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. Patients and methodsPaediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h of treatment and after 72 h. ResultsEleven (22.9%) out of 48 patients admitted due to COVID-19 (March–July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs 416.5 ms (29.4), (P = .716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms [IQR 48.7] (P = .062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. ConclusionsThe use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc > 500 ms.

Influence of baseline QTc on sotalol-induced prolongation of ventricular repolarization in men and women.

The extent of sotalol-induced QTc prolongation on the electrocardiogram, is variable among subjects and influenced by sex. However, the influence of baseline QTc on the extent of drug-induced QTc prolongation remains unclear. This was studied around peak plasma concentration in a large cohort of 376 healthy male and 614 healthy female subjects who received 80 mg of sotalol orally. Baseline QTc was 379 ± 16 ms in men and 393 ± 15 ms in women (P< .0001). The change in QTc from baseline was highly variable among both sexes and was greater in women than in men (26.5± 13.2 vs.13.0±10.8ms; P< .0001). The slope of the regression line between QTc on sotalol and baseline QTc did not significantly differ from unity in men and in women, indicating that the extent of QTc prolongation with sotalol was not influenced by baseline QTc. Assessing QTc after administration of an IKr blocker may be more important than measuring a baseline QTc.

ECG changes in psychiatric patients on psychotropic medications

Abstract Funding Acknowledgements Type of funding sources: None. Background Suicide and euthanasia accounts for 14.3% of deaths in those with psychiatric conditions. The rest are attributed to preventable causes such as cardiovascular disease, respiratory disease, and infections. Several psychotropic medications have been associated with sudden death due to their effect on prolonging QT interval, resulting in the development of a polymorphic ventricular arrhythmia, Torsades de Pointes (TdP). TdP may be self-limiting or lead to sudden cardiac arrest and death. Purpose This study aims to evaluate the cardiotoxic effects of psychotropic medications. Method This is a descriptive retrospective study of patients submitted to the local psychiatric wards within one year. Patients with psychotropic drug prescriptions were included while patients below 18 years old, pregnant, or did not have ECG performed were excluded. The control group consisted of sex- and age- matched patients with ECG conducted for occupational health purposes. Multiple regression models were conducted to investigate the predictors of significant ECG differences. Result Of the 154 psychiatric inpatients admitted, exclusions were 44 patients due to exclusion criteria and 19 patients due to difficulty in physical file access. The study population (n = 91) had a mean age of 36.7 years old with 40.7% female and 59.3% male. The predominant diagnoses were schizophrenia and delusional disorders (58.2%). 86 psychiatric patients (94.5%) were prescribed antipsychotic drugs (APD). A significantly higher proportion of psychiatric patients has a history of smoking (p &amp;lt; 0.001), alcohol consumption (p = 0.001), and illicit drug use (p &amp;lt; 0.001). They also exhibited significantly more co-morbid illnesses including hypertension (p = 0.022), hyperlipidaemia (p = 0.013), diabetes (p = 0.026) and thyroid disease (p = 0.023) than the control population. Psychiatric patients had a significantly higher mean heart rate (79.9 vs 69.6 ms; p &amp;lt; 0.001) and QTc interval (452.2 vs 418.6ms; p &amp;lt; 0.001). Mean QTc interval was significantly longer for psychiatric patients in both male (454.2 vs 414.5ms; p &amp;lt; 0.001) and female (449.3 vs 425.6 ms; p = 0.029) gender. Psychotropic drug use is a significant predictor for both prolonged heart rate (p &amp;lt; 0.001) and prolonged QTc interval (p &amp;lt; 0.001). Electrolyte imbalance is a significant predictor of prolonged QTc interval only (p = 0.036). One year follow of both groups detected only 1 psychiatric patient with palpitation. Conclusion Psychiatric patients on psychotropic medications have a longer baseline heart rate and QTc interval, which was not associated with MACE at 1 year. None of the underlying comorbidities and lifestyle choices were significant predictors of this. Electrolyte abnormalities and psychotropic drug use significantly predicted QTc prolongation. However, these findings were largely driven by APD use. A follow-up study of a longer period is recommended to investigate whether patients with prolonged QTc interval are of higher risk of MACE occurrence.

Changes in QTc interval after hydroxychloroquine therapy in patients with COVID-19 infection: a large, retrospective, multicentre cohort study

ObjectiveTo evaluate the extent of hydroxychloroquine-induced corrected QT (QTc) prolongation and its relation to COVID-19 infection severity and incidence of polymorphic ventricular arrhythmias and sudden arrhythmic deaths.DesignA large-scale cohort study...

Cardiotoxicity of azithromycin in COVID-19: an overall proportion meta-analysis.

To explore the incidence of pro-arrhythmic effects such as corrected QT interval (QTc) prolongation, arrhythmic events and myocardial injury of azithromycin as administered for the treatment of COVID-19. We searched PubMed, the Cochrane Library and Web of Science databases from inception to 18 January 2021, as well as the medRχiv preprint database from 1 August 2020 to 18 January 2021, for studies exploring the cardiotoxicity effects of azithromycin, with or without concomitant use of hydroxychloroquine, in the context of Covid19. We performed a random effects single-arm meta-analysis of studies to calculate pooled proportion estimates for pro-arrhythmic effects. Meta-regression analyses were conducted to explain between-study heterogeneity. Thirty-four studies with a total of 3088 patients were included. Among 12 studies, the incidence of > 60ms QTc prolongation from baseline was 13% (95% CI 9%-18%, I² = 73%), whereas, among 28 studies, the incidence of QTc ≥ 500 ms at follow-up was 8% (95% CI 6%-11%, I² = 78%). Still, the discontinuation rate due to QTc prolongation was only 3% (95% CI 2%-5%, I² = 55%). The absolute risk of Torsade de pointes and ventricular tachycardia was 0.2% and 0.8%, respectively. Increased age, male sex, presence of hypertension or diabetes mellitus, use of QTc prolonging medication, prolonged baseline QTc interval and indicators of disease severity such as death explained between-study heterogeneity. Azithromycin, with or without hydroxychloroquine, leads to a significant risk for critical QTc prolongation in patients with Covid19. Due to its cardiotoxicity effects and its unproven efficacy in Covid19, azithromycin use should be limited to cases of bacterial co-infection.

Evaluation of Corrected QT Intervals of 74 COVID19 Patients Treated with Hydroxychloroquine in Combination with or without Azithromycin and/or Favipiravir

Objective: We aimed to evaluate the degree of QTc prolongation and associated factors in patients with COVID-19 in association with their usage of hydroxychloroquine (HCQ) with or without the combination of azithromycin (AZ) and/or favipiravir (FAV). Methods: This single-center, retrospective study was conducted in a tertiary care university hospital. We retrospectively examined the pre- and post-treatment electrocardiogram (ECG) records of 74 patients. Results: The median age was 44 (interquartile range [IQR] 27), and 34 (45.5%) of them were women. All these 74 patients were treated with HCQ. Sixty-three of them (83.2%) were treated with AZ, and eight patients (10.8%) also were treated with plus favipiravir. All ECGs were in sinus rhythm, and arrhythmia was not developed in any patients. The median (IQR) baseline QTc of 74 patients was 400 (375- 421) milliseconds, the median (IQR) post-treatment QTc was 418 milliseconds (391-432), and the change was statistically significant (P &lt; .001). There was no statistically significant difference in QTc prolongation between treatment groups. In the linear regression model, moderate disease activity, higher Modified Early Warning Score (MEWS) score (2), and heart rate were independent predictors. QTc prolongation of more than 60 milliseconds was observed in five patients (6.7%). Post-treatment QTc value of over 500 milliseconds was observed in three patients (4%), and the drugs were discontinued. Conclusions: This is the first study that demonstrates that MEWS score and disease severity are related to higher QTc prolongation values. HCQ, AZ, and FAV should be safely used in patients with lower MEWS score and without the severe disease, in conjunction with QTc follow-up.

Prognostic Significance of Prolonged Corrected QT Interval in Acute Ischemic Stroke.

Background and Purpose: The aim of this study was to determine the relationship between the heart rate-corrected QT (QTc) interval and the risk of incident long-term mortality in patients with acute ischemic stroke (AIS), considering the impact of sex differences on clinical characteristics, outcomes, and QTc intervals.Methods: We analyzed prospectively registered data included patients with AIS who visited the emergency room within 24 h of stroke onset and underwent routine cardiac testing, such as measurements of cardiac enzymes and 12-lead ECG. QTc interval was corrected for heart rate using Fridericia's formula and was stratified by sex-specific quartiles. Cox proportional hazards models were used to examine the association between baseline QTc interval and incident all-cause death.Results: A total of 1,668 patients with 1,018 (61.0%) men and mean age 66.0 ± 12.4 years were deemed eligible. Based on the categorized quartiles of the QTc interval, cardiovascular risk profile, and stroke severity increased with prolonged QTc interval, and the risk of long-term mortality increased over a median follow-up of 33 months. Cox proportional hazard model analysis showed that the highest quartile of QTc interval (≥479 msec in men and ≥498 msec in women; hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.07–2.08) was associated with all-cause death. Furthermore, dichotomized QTc interval prolongation, defined by the highest septile of the QTc interval (≥501 ms in men and ≥517 m in women: HR: 1.33, 95% CI: 1.00–1.80) was significantly associated with all-cause mortality after adjusting for all clinically relevant variables, such as stroke severity.Conclusions: Prolonged QTc interval was associated with increased risk of long-term mortality, in parallel with the increasing trend of prevalence of cardiovascular risk profiles and stroke severity, across sex differences in AIS patients.