Effect of Replacing Vendor QTc Alerts with a Custom QTc Risk Alert in Inpatients

Objective The aim of the study is to implement a customized QTc interval clinical decision support (CDS) alert strategy in our electronic health record for hospitalized patients and aimed at providers with the following objectives: minimize QTc prolongation, minimize exposure to QTc prolonging medications, and decrease overall QTc-related alerts. A strategy that was based on the validated QTc risk scoring tool and replacing medication knowledge vendor alerts with custom QTc prolongation alerts was implemented. Methods This is a retrospective quasi-experimental study with a pre-intervention period (August 2019 to October 2019) and post-intervention period (December 2019 to February 2020). The custom alert was implemented in November 2019. Results In the pre-implementation group, 361 (19.3%) patients developed QTc prolongation, and in the post-implementation group, 357 (19.6%) patients developed QTc prolongation (OR: 1.02, 95% CI: 0.87–1.20, p = 0.81). The odds ratio of an action taken post-implementation compared with pre-implementation was 18.90 (95% CI: 14.03–25.47, p <0. 001). There was also a decrease in total orders for QTc prolonging medications from 7,921 (5.5%) to 7,566 (5.3%) with an odds ratio of 0.96 (95% CI: 0.93–0.99, p = 0.01). Conclusion We were able to decrease patient exposure to QTc prolonging medications while not increasing the rate of QTc prolongation as well as improving alert action rate. Additionally, there was a decrease in QTc prolonging medication orders which illustrates the benefit of using a validated risk score with a customized CDS approach compared with a traditional vendor-based strategy. Further research is needed to confirm if an approach implemented at our organization can reduce QTc prolongation rates.

QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection

Background: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population. Methods: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms). Results: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation ( P = .004 for the likelihood-ratio test). Conclusion: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.

Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men

Background Systemic inflammation and male hypogonadism are 2 increasingly recognized “nonconventional” risk factors for long‐QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate–corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men. We hypothesized that, during inflammatory activation in men, testosterone levels decrease and that this enhances TdP risk by contributing to the overall prolonging effect of inflammation on QTc. Methods and Results We investigated (1) the levels of sex hormones and their relationship with inflammatory markers and QTc in male patients with different types of inflammatory diseases, during active phase and recovery; and (2) the association between inflammatory markers and sex hormones in a cohort of male patients who developed extreme QTc prolongation and TdP, consecutively collected over 10 years. In men with active inflammatory diseases, testosterone levels were significantly reduced, but promptly normalized in association with the decrease in C‐reactive protein and interleukin‐6 levels. Reduction of testosterone levels, which also inversely correlated with 17‐β estradiol over time, significantly contributed to inflammation‐induced QTc prolongation. In men with TdP, both active systemic inflammation and hypogonadism were frequently present, with significant correlations between C‐reactive protein, testosterone, and 17‐β estradiol levels; in these patients, increased C‐reactive protein and reduced testosterone were associated with a worse short‐term outcome of the arrhythmia. Conclusions During systemic inflammatory activation, interleukin‐6 elevation is associated with reduced testosterone levels in males, possibly deriving from an enhanced androgen‐to‐estrogen conversion. While transient, inflammatory hypotestosteronemia is significantly associated with an increased long‐QT syndrome/TdP risk in men.

QTc Intervals Are Prolonged in Late Preterm and Term Neonates during Therapeutic Hypothermia but Normalize Afterwards

Background: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker for pharmacovigilance during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. Methods: A structured search and literature assessment (PubMed, Embase, and Google Scholar) with ‘Newborn/Infant, QT and hypothermia’ was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1–7). Results: We retrieved 94 QTc intervals (during TH (n = 50, until day 3) or subsequent normothermia (n = 44, day 4–7)) in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430–678), and 410 (317–540) ms afterwards (difference 98 ms, or +28 ms/°C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. Conclusions: We highlighted a relevant non-maturational covariate (°C dependent TH) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.

Development and Validation of a QTc-Prolongation Risk Score to Optimize Interruptive Medication Alerts

Introduction: Drug-drug interaction (DDI) warnings are employed in many institutions when more than one QTc-prolonging medication is prescribed; however, this leads to alert fatigue where alerts are frequently overridden by clinicians due to patient non-specificity or low risk. This study aimed at reducing alert fatigue through developing a custom alert triggered by a patient-specific QTc-prolongation risk score, and validating it against database-driven DDI warnings for QTc prolongation. Methods and Results: Between November 23, 2019 and January 31, 2020, inpatients with a baseline and a follow-up 12-lead ECG reading within 14 days were identified. Each time a QTc-prolonging medication order was signed or verified, the QTc-prolongation risk score was calculated in the electronic health record (EHR), triggering a custom alert in the background. Follow-up 12-lead ECG readings were used to calculate sensitivity and specificity for both the custom alert and the DDI warning. A total of 100 patients had a risk score calculation and were included in our analysis, representing 521 custom alerts and 449 DDI warnings. The preliminary QTc-prolongation risk score did not achieve a reduction in false positive alerts with a cutoff of 10 points. A multiple logistic regression was performed to re-arrange the components and optimize the risk score. Conclusion: Our adjusted QTc-prolongation risk score, with a cutoff of 5 points, achieved a specificity of 66% and a negative predictive value of 83%. These results will allow us to integrate the risk score into the EHR as a guidance tool to predict QTc-prolongation.

A study of serum calcium level in cases of malaria in a tertiary care hospital

Background: Malaria is a tropical disease caused by Plasmodium species, commonly P. falciparum and P. vivax. Carpopedal spasm has been noted in many patients presenting with malarial fever. Most of the patients are later found to have hypocalcaemia. Hypocalcaemia associated with malaria can cause many clinical manifestations, including life threatening conditions such as arrhythmias, convulsions etc.Methods: A cross-sectional study was conducted with the aim to determine the prevalence and clinical profile of hypocalcaemia in different types of malarial fever. 88 patients of malarial fever were studied. Patients were stratified according to the species of plasmodium and into complicated and uncomplicated malaria. Total serum calcium level and QTc interval were analysed in each patient. Data collected were analysed.Results: Prevalence of hypocalcaemia in malaria was found to be 54.45% in our study. Hypocalcaemia was more prevalent in complicated malaria than uncomplicated malaria. Complicated falciparum malaria showed highest prevalence of hypocalcaemia. Status of complexity of malaria was not found to be related to occurrence of hypocalcaemia in any types of malaria. Prevalence of QTc prolongation in malaria was found to be 48.46%. Prevalence of QTc prolongation was found to be more in complicated malaria than uncomplicated malaria. QTc prolongation was most prevalent in complicated falciparum malaria. 83.3% of those with QTc prolongation had hypocalcaemia.Conclusions: Hypocalcemia and QTc prolongation were more prevalent in complicated malaria than in uncomplicated malaria. Both Hypocalcaemia and QTc prolongation were most prevalent in complicated falciparum malaria.

QTc Intervals Are Prolonged in Late Preterm and Term Neonates During Therapeutic Hypothermia but Normalize Afterwards

Background: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker to assess safety during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. Methods: A structured search and literature assessment (PubMed, Embase, Google Scholar) with &lsquo;Newborn/Infant, QT and hypothermia&rsquo; was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1-7). Results: We retrieved 94 QTc intervals [during TH (n=50, until day 3) or subsequent normothermia (n=44, day 4-7)] in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430-678), and 410 (317-540) ms afterwards (difference 98 ms, or +28 ms/&deg;C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. Conclusions: We added a relevant non-maturational covariate (TH, &deg;C dependent) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.