Dataset Information

The Clinical Utility of Continuous QT Interval Monitoring in Patients Admitted With COVID-19 Compared With Standard of Care: A Prospective Cohort Study.

ABSTRACT: Background:QT interval monitoring has gained much interest during the COVID-19 pandemic because of the use of QT-prolonging medications and the concern about viral transmission with serial electrocardiograms (ECGs). We hypothesized that continuous telemetry-based QT monitoring is associated with better detection of prolonged QT episodes. Methods:We introduced continuous cardiac telemetry (CCT) with an algorithm for automated QT interval monitoring to our designated COVID-19 units. The daily maximum automated heart rate-corrected QT (Auto-QTc) measurements were recorded. We compared the proportion of marked QTc prolongation (Long-QTc) episodes, defined as QTc ? 500 ms, in patients with suspected or confirmed COVID-19 who were admitted before and after CCT was implemented (control group vs CCT group, respectively). Manual QTc measurement by electrophysiologists was used to verify Auto-QTc. Charts were reviewed to describe the clinical response to Long-QTc episodes. Results:We included 33 consecutive patients (total of 451 monitoring days). Long-QTc episodes were detected more frequently in the CCT group (69/206 [34%] vs 26/245 [11%]; P < 0.0001) and ECGs were performed less frequently (32/206 [16%] vs 78/245 [32%]; P < 0.0001). Auto-QTc correlated well with QTc measurement by electrophysiologists with an excellent agreement in detecting Long-QTc (? = 0.8; P < 0.008). Only 28% of patients with Long-QTc episodes were treated with recommended therapies. There was 1 episode of torsade de pointes in the control group and none in the CCT group. Conclusions:Continuous QT interval monitoring is superior to standard of care in detecting episodes of Long-QTc with minimal need for ECGs. The clinical response to Long-QTc episodes is suboptimal.

SUBMITTER: Alqarawi W

PROVIDER: S-EPMC7374138 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The Clinical Utility of Continuous QT Interval Monitoring in Patients Admitted With COVID-19 Compared With Standard of Care: A Prospective Cohort Study.

Alqarawi Wael W Birnie David H DH Golian Mehrdad M Nair Girish M GM Nery Pablo B PB Klein Andres A Davis Darryl R DR Sadek Mouhannad M MM Neilipovitz David D Johnson Christopher B CB Green Martin S MS Redpath Calum C

CJC open 20200722 6

<h4>Background</h4>QT interval monitoring has gained much interest during the COVID-19 pandemic because of the use of QT-prolonging medications and the concern about viral transmission with serial electrocardiograms (ECGs). We hypothesized that continuous telemetry-based QT monitoring is associated with better detection of prolonged QT episodes.<h4>Methods</h4>We introduced continuous cardiac telemetry (CCT) with an algorithm for automated QT interval monitoring to our designated COVID-19 units. ...[more]

PMID: 32838256

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Project description:The effects on ventricular repolarization-recorded on the electrocardiogram (ECG) as lengthening of the QT interval-of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero. ECGs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; "control") or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries. Drug levels were measured at steady state (month 1) in a subset of patients. We compared treatment effects on the QTc and modeled the effect of individual drugs' maximum concentrations of drug in serum (Cmax) on the Fridericia-corrected QT interval. A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline (mean age, 30.7 years; 27% female). Median heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5°C. Pretreatment, the nonlinear model estimated the best correction factor at 0.4081 in between Bazett's (0.5) and Fridericia's (0.33) corrections. On treatment, Fridericia (QTcF) was the best correction factor. A total of 1,602 patients contributed to the analysis of QTcF by treatment arm. The peak QTcF value during follow-up was >480 ms for 21 patients (7 and 14 in the test and control arms, respectively) and >500 ms for 9 patients (5 and 4, respectively), corresponding to a risk difference of -0.9% (95% confidence interval [CI], -2.0% to 2.3%; P = 0.12) and 0.1% (95% CI, -0.6% to 0.9%; P = 0.75), respectively, between the test and control arms. One hundred six (6.6%) patients had a peak measurement change from baseline of >60 ms (adjusted between-arm difference, 0.8%; 95% CI, -1.4% to 3.1%; P = 0.47). No evidence was found of an association between Cmax of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a standard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis. This is to date the largest data set studying the effects of antituberculosis regimens on the QT, both for the standard regimen and for a fluoroquinolone-containing regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT00216385.).

Project description:Genome-wide association studies (GWAS) have suggested that sequence variation in cis-regulatory elements (CREs) modulate common disease risk and trait variation. However, identification of the majority of these causal variants and their mechanism of action have remained significant challenges. We used reporter assays for all common variants at the QT interval associated SCN5A GWAS locus with the goal of identifying causal variants for the association. A target region of ~500kb containing SCN5A was defined based on recombination hotspots (rate>10cM/Mb; estimated from HapMap) flanking the 5 independent QT interval GWAS hits. Within this region, all common variants (minor allele frequency >5%), from the 1000 Genomes European ancestry populations, in moderate linkage disequilibrium (LD; r2>0.3) with any of the 5 sentinel hits, were selected for analyses. Of a total 121 variants selected, 112 variants in 104 amplicons passed primer design (amplicon size 256-617bp; median 397bp), with both alleles of 106 variants successfully cloned along with flanking sequences into 98 amplicons upstream of a minimal promoter-driven firefly luciferase gene in pGL4.23. Cardiomyocyte cells, AC16 (human) and HL1 (mouse), were transfected with test constructs and Renilla luciferase vector (for transfection normalization) in triplicate; luciferase assays were performed 24h later. All cloning and reporter assays were performed in 96- and 24-well plates. In reporter assays across the two cell lines, compared to empty vector, 37 amplicons showed enhancer activity (z-score>99 %tile), with a concordance rate of ~70%. Of these 37 enhancer CREs, 9 overlapped open chromatin regions (DNase-seq peaks) observed in adult human heart tissue, largest among all human tissues evaluated by the RoadMap Epigenomics project. Of these 37 enhancer CREs, 12 showed allelic difference in reporter activity (P<0.05), thus identifying at least one enhancer CRE variant in high-to-moderate LD with each of the 5 sentinel hits. Using GTEx heart left ventricle (n=190) gene expression data, we showed correlation between SCN5A expression and the number of QT interval prolonging alleles across the 5 index SNPs. We are currently assessing the binding of cardiac nuclear factors at the 12 enhancer CRE variants by gel-shift assays and the effect of CRISPR-Cas9 mediated CRE deletion on SCN5A expression in AC16 and HL1 cells, an analyses helped by evaluation of AC16 and HL1 cells by RNA-seq, ATAC-seq and karyotyping. Thus, independent of the publicly available epigenomic data, which are of limited cell-type relevance, an unbiased in vitro reporter screen for CREs overlapping all common variants associated with QT interval at the SCN5A GWAS locus identified 12 common cis-regulatory variants that map to cardiac open chromatin regions and correlate with SCN5A cardiac expression.

Dataset Information

The Clinical Utility of Continuous QT Interval Monitoring in Patients Admitted With COVID-19 Compared With Standard of Care: A Prospective Cohort Study.

Publications

The Clinical Utility of Continuous QT Interval Monitoring in Patients Admitted With COVID-19 Compared With Standard of Care: A Prospective Cohort Study.

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