Aims: Hydroxychloroquine and chloroquine ([hydroxy]chloroquine) are drugs used to treat malaria and rheumatological disorders and were recently suggested as beneficial for prevention and treatment of patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. However, longitudinal studies to assess the electrocardiographic and cardiotoxic effects of these drugs are limited. In this study, we aimed to investigate the effect of these drugs on QTc-interval and incidence of sudden cardiac death (SCD). Methods We designed a longitudinal follow-up study of individuals within the prospective population-based Rotterdam Study. Eligible individuals had available data on medication and repeated ECG measurements. The study period was between 1 January 1991 and 1 January 2014. We studied on current and past use of [hydroxy]chloroquine as a time-varying exposure; high versus low daily dose of [hydroxy]chloroquine. QTc-interval duration, and the occurrence of SCD were the main outcomes. SCD was defined as an unexpected and sudden death due to cardiac arrhythmia within one hour of the onset of acute symptoms, and in patients without cardiac symptoms within 24 hours before death. Results Among the study population of 14 594 individuals (58.8% women) with an average age of 65 years, 346 patients used [hydroxy]chloroquine at any time during follow-up. The total number of SCD cases was 609. In a multiple linear mixed model analysis, the current use of [hydroxy]chloroquine was associated with a significantly increased duration of the QTc-interval of 8.1 ms (95% CI: 3.6; 12.6) compared with non-users. The association was stronger among current-high daily dosage [15.3 (95%CI: 7.0; 23.6)] compared with current-low daily dosage [5.5 (95%CI: 0.4; 10.7)] users. In a Cox proportional hazard regression analysis, the risk of SCD was significantly higher in participants who were current users of [hydroxy]chloroquine than in non-users [adjusted hazard ratio; 3.7 (95%CI: 1.1; 12.6)]. Conclusions In this longitudinal study, persons who received [hydroxy]chloroquine had an increased QTc-interval duration and the association was dose-dependent. [Hydroxy]chloroquine was associated with a significantly increased risk of SCD. As long as their activity against COVID-19 is controversial, cardiotoxicity is a strong argument against using these drugs to treat COVID-19 infections.
Background: Whether liraglutide use improves cardiometabolic risk factors in different subsets of subjects with coronary artery disease (CAD) remains unclear. In a systematic review and meta-analysis, we quantified the effects of liraglutide on cardiometabolic risk profile in subjects with CAD with or without type 2 diabetes mellitus (T2D).Methods: Online database searches were conducted in PubMed, Scopus, EMBASE, Web of Science, Cochrane library, and Google Scholar from incept up to 15th January 2021. We identified randomized controlled trials (RCTs) assessing the effects of liraglutide compared to placebo on cardiometabolic risk profile. We used the random- or fixed-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs).Results: Out of a total of 7,320 citations, six articles (seven RCTs) with 294 subjects with CAD (mean age, 61.21 years; 19% women) were included. Our findings presented as WMD and 95% CI showed a statistical significant decrease in hemoglobin A1c (HbA1c) [−0.36%; −0.47; −0.26, p < 0.001; I2 = 0.0% (with 6 RCTs)], body mass index (BMI) [−0.61 kg/m2; −1.21; −0.01, p = 0.047; I2 = 72.2% (with five RCTs)], and waist circumference [−2.41 cm; −3.47; −1.36, p < 0.001; I2 = 0.0% (with three RCTs)]. Through a set of subgroup analyses, we found a significant reduction in BMI in CAD patients with T2D [WMD = −1.06; 95% CI, −1.42, −0.70, p < 0.001; I2 = 0.0% (with three RCTs)] compared to CAD only patients [WMD = −0.08; 95% CI, −0.45, 0.29, p = 0.66; I2 = 0.0% (with two RCTs)] in the liraglutide group compared with the placebo group. No significant changes in heart rate, blood pressure, and lipid profiles were observed.Conclusions: Among people with established CAD, liraglutide significantly improved HbA1c, BMI, and waist circumference values. The effect of liraglutide on BMI was more robust in individuals with T2D compared to those without.
The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
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