Can the introduction of a 12-lead ECG help reduce mortality in those presenting with foot ulceration to multidisciplinary diabetic foot clinics? An observational evaluation of a real-world implementation pilot in England.

AIMS/HYPOTHESIS: The risk of dying within 2 years of presentation with diabetic foot ulceration is over six times the risk of amputation, with CVD the major contributor. Using an observational evaluation of a real-world implementation pilot, we aimed to assess whether for those presenting with diabetic foot ulceration in England, introducing a 12-lead ECG into routine care followed by appropriate clinical action was associated with reduced mortality. METHODS: Between July 2014 and December 2017, ten multidisciplinary diabetic foot services in England participated in a pilot project introducing 12-lead ECGs for new attendees with foot ulceration. Inception coincided with launch of the National Diabetes Footcare Audit (NDFA), whereby all diabetic footcare services in England were invited to enter data on new attendees with foot ulceration. Poisson regression models assessed the mortality RR at 2 and 5 years following first assessment of those receiving care in a participating pilot unit vs those receiving care in any other unit in England, adjusting for age, sex, ethnicity, deprivation, type and duration of diabetes, ulcer severity, and morbidity in the year prior to first assessment. RESULTS: Of the 3110 people recorded in the NDFA at a participating unit during the pilot, 33% (1015) were recorded as having received an ECG. A further 25,195 people recorded in the NDFA had attended another English footcare service. Unadjusted mortality in the pilot units was 16.3% (165) at 2 years and 37.4% (380) at 5 years for those who received an ECG, and 20.5% (430) and 45.2% (950), respectively, for those who did not receive an ECG. For people included in the NDFA at other units, unadjusted mortality was 20.1% (5075) and 42.6% (10,745), respectively. In the fully adjusted model, mortality was not significantly lower for those attending participating units at 2 (RR 0.93 [95% CI 0.85, 1.01]) or 5 years (RR 0.95 [95% CI 0.90, 1.01]). At participating units, mortality in those who received an ECG vs those who did not was lower at 5 years (RR 0.86 [95% CI 0.76, 0.97]), but not at 2 years (RR 0.87 [95% CI 0.72, 1.04]). Comparing just those that received an ECG with attendees at all other centres in England, mortality was lower at 5 years (RR 0.87 [95% CI 0.78, 0.96]), but not at 2 years (RR 0.86 [95% CI 0.74, 1.01]). CONCLUSIONS/INTERPRETATION: The evaluation confirms the high mortality seen in those presenting with diabetic foot ulceration. Overall mortality at the participating units was not significantly reduced at 2 or 5 years, with confidence intervals just crossing parity. Implementation of the 12-lead ECG into the routine care pathway proved challenging for clinical teams-overall a third of attendees had one, although some units delivered the intervention to over 60% of attendees-and the evaluation was therefore underpowered. Nonetheless, the signals of potential mortality benefit among those who had an ECG suggest that units in a position to operationalise implementation may wish to consider this. DATA AVAILABILITY: Data from the National Diabetes Audit can be requested through the National Health Service Digital Data Access Request Service process at: https://digital.nhs.uk/services/data-access-request-service-dars/dars-products-and-services/data-set-catalogue/national-diabetes-audit-nda.

Ivosidenib significantly reduces triazole levels in patients with acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND: Ivosidenib is primarily metabolized by CYP3A4; however, it induces CYP450 isozymes, including CYP3A4 and CYP2C9, whereas it inhibits drug transporters, including P-glycoprotein. Patients with acute myeloid leukemia are at risk of invasive fungal infections, and therefore posaconazole and voriconazole are commonly used in this population. Voriconazole is a substrate of CYP2C9, CYP2C19, and CYP3A4; therefore, concomitant ivosidenib may result in decreased serum concentrations. Although posaconazole is a substrate of P-glycoprotein, it is metabolized primarily via UDP glucuronidation; thus, the impact of ivosidenib on posaconazole exposure is unknown. METHODS: Patients treated with ivosidenib and concomitant triazole with at least one serum trough level were included. Subtherapeutic levels were defined as posaconazole <700 ng/mL and voriconazole <1.0 µg/mL. The incidences of breakthrough invasive fungal infections and QTc prolongation were identified at least 5 days after initiation of ivosidenib with concomitant triazole. RESULTS: Seventy-eight serum triazole levels from 31 patients receiving ivosidenib-containing therapy and concomitant triazole were evaluated. Of the 78 concomitant levels, 47 (60%) were subtherapeutic (posaconazole: n = 20 of 43 [47%]; voriconazole: n = 27 of 35 [77%]). Compared to levels drawn while patients were off ivosidenib, median triazole serum levels during concomitant ivosidenib were significantly reduced. There was no apparent increase in incidence of grade 3 QTc prolongation with concomitant azole antifungal and ivosidenib 500 mg daily. CONCLUSIONS: This study demonstrated that concomitant ivosidenib significantly reduced posaconazole and voriconazole levels. Voriconazole should be avoided, empiric high-dose posaconazole (>300 mg/day) may be considered, and therapeutic drug monitoring is recommended in all patients receiving concomitant ivosidenib.

Utilizing median and maximum QTc values improves prediction of breakthrough cardiac events in pediatric long QT syndrome.

INTRODUCTION: Although prior studies indicate that a QTc > 500 ms on a single baseline 12-lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS. METHODS: We performed a retrospective analysis of 433 patients with LQTS evaluated, risk-stratified, and undergoing active guideline-based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF-terminating ICD shock, and sudden cardiac death (SCD). RESULTS: During the median follow-up of 5.5 years (interquartile range [IQR] = 3-9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c-statistic = 0.93-0.95). Patients in the high-risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%-81%) when compared to patients in both medium-risk (93%-97%) and low-risk (98%-99%) groups. CONCLUSIONS: The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12-lead ECGs are at the highest risk of BCE while on guideline-directed medical therapy.

Use of portable single-lead electrocardiogram device as an alternative for QTc monitoring in critically ill patients.

PURPOSE: Acquired QT prolongation is frequent and leads to a higher mortality rate in critically ill patients. KardiaMobile 1L® (KM1L) is a portable, user-friendly single lead, mobile alternative to conventional 12-lead electrocardiogram (12-L ECG) that could be more readily available, potentially facilitating more frequent QTc assessments in intensive care units (ICU); however, there is currently no evidence to validate this potential use. METHODS: We conducted a prospective diagnostic test study comparing QT interval measurement using KM1L with conventional 12-L ECG ordered for any reason in patients admitted to an ICU. We compared the mean difference using a paired t-test, agreement using Bland-Altman analysis, and Lin's concordance coefficient, numerical precision (proportion of QT measurements with <10 ms difference between KM1L and conventional 12-L ECG), and clinical precision (concordance for adequate discrimination of prolonged QTc). RESULTS: We included 114 patients (61.4% men, 60% cardiovascular etiology of hospitalization) with 131 12-L ECG traces. We found no statistical difference between corrected QT measurements (427 ms vs. 428 ms, p = .308). Lin's concordance coefficient was 0.848 (95% CI 0.801-0.894, p = .001). Clinical precision was excellent in males and substantial in females (Kappa 0.837 and 0.781, respectively). Numerical precision was lower in patients with vasoactive drugs (-13.99 ms), QT-prolonging drugs (13.84 ms), antiarrhythmic drugs (-12.87 ms), and a heart rate (HR) difference of ≥5 beats per minute (bpm) between devices (-11.26 ms). CONCLUSION: Our study validates the clinical viability of KM1L, a single-lead mobile ECG device, for identifying prolonged QT intervals in ICU patients. Caution is warranted in patients with certain medical conditions that may affect numerical precision.

Meta-analysis application to hERG safety evaluation in clinical trials.

One objective of meta-analysis, which synthesizes evidence across multiple studies, is to assess the consistency and investigate the heterogeneity across studies. In this project, we performed a meta-analysis on moxifloxacin (positive control in QT assessment studies) data to characterize the exposure-response relationship and determine the safety margin associated with 10-msec QTc effects for moxifloxacin based on 26 thorough QT studies submitted to the FDA. Multiple meta-analysis methods were used (including two novel methods) to evaluate the exposure-response relationship and estimate the critical concentration and the corresponding confidence interval of moxifloxacin associated with a 10-msec QTc effect based on the concentration-QTc models. These meta-analysis methods (aggregate data vs. individual participant data; fixed effect vs. random effect) were compared in terms of their precision and robustness. With the selected meta-analysis method, we demonstrated the homogeneity and heterogeneity of the moxifloxacin concentration-QTc relationship in studies. We also estimated the critical concentration of moxifloxacin that can be used to calculate the hERG safety margin of this drug.

Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study.

Nifekalant hydrochloride is a class III antiarrhythmic agent which could increase the duration of the action potential and the effective refractory period of ventricular and atrial myocytes by blocking the K+ current. Nifekalant is used to prevent ventricular tachycardia/ventricular fibrillation. QT interval prolongation is the main measurable drug effect. However, due to the complicated dosing plan in clinic, the relationship among dosage, time, drug concentration and efficacy is not fully understood. In this study, a single-center, randomized, blind, dose-ascending, placebo-controlled study was conducted to explore the intrinsic characteristics of nifekalant injection in healthy Chinese volunteers by a population pharmacokinetic (PK)-pharmacodynamic (PD) model approach. 42 subjects were enrolled in this study and received one of three dose plans (loading dose on Day 1 (0.15, 0.3 or 0.5 mg/kg), loading dose followed by maintenance dose (0.2, 0.4 or 0.8 mg/kg/h) on Day 4) or vehicle. Blood samples were drawn for PK evaluation, and ECGs were recorded for QTc calculation at the designed timepoints. No Torsades de Pointes occurred during the study. The popPK model of nifekalant injection could be described by a two-compartment model with first-order elimination. The population mean clearance (CL) was 53.8 L/h. The population mean distribution volume of the central (Vc) and peripheral (Vp) compartments was 8.27 L and 45.6 L, respectively. A nonlinear dose-response (Emax) model well described the pharmacodynamic effect (QTc interval prolongation) of nifekalant. The Emax and EC50 from current study were 101 ms and 342 ng/mL, respectively.

Factors associated with prolonged QTc interval in Iranian population: MASHAD cohort study.

AIM: QTc interval prolongation is a growing global issue which can cause torsades de pointes, a potentially fatal arrhythmia. We aimed to identify risk factors for prolonged QT interval in men and women. METHODS: The Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study collected electrocardiogram interval data. QT was corrected for heart rate using the Bazett's formula. Ordinal logistic regression with crude (univariable) and adjusted (multivariate) association analyses in the form of odds ratio and corresponding 95% confidence interval (CI) were used to identify the factors associated with QTc prolongation. RESULTS: A total of 8878 individuals including 5318 females and 3560 males, aged 35 to 65 years, were included in this cross-sectional study. Participants with QTc prolongation were more likely to be older and have hypercholesterolemia, hypertension (HTN), and Type 2 diabetes mellitus (T2DM), but to have lower levels of physical activity (P < 0.05). Age (OR = 1.68, 95%CI = 1.18-2.39), hypercholesterolemia (OR = 1.77, 95%CI = 1.24-2.51), HTN (OR = 1.36, 95%CI = 1.06-1.73), T2DM (OR = 1.59, 95%CI = 1.19-2.13), severe anxiety (OR = 1.80, 95%CI = 1.05-3.11) and mild depression (OR = 1.38, 95%CI = 1.01-1.88) were independent risk factors for prolonged QTc interval in men. For women, only HTN (OR = 1.29, 95%CI = 1.02-1.63) and T2DM (OR = 1.50, 95%CI = 1.14-1.97) were independent risk factors. CONCLUSIONS: Older age, Hypercholesterolemia, HTN, T2DM, severe anxiety and mild depression in men, and HTN and T2DM in women were associated with high risk of prolonged QTc interval. Healthcare practitioners should be aware of the risk factors of QTc interval prolongation and should exercise caution in the management of certain patients.

QTc intervals at rest and during exercise assessed by group correction formulas in survivors of childhood acute lymphoblastic leukemia.

INTRODUCTION: Early 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. METHODS: Two 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. RESULTS: The 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%). CONCLUSION: This 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.

Electrocardiographic proarrhythmic changes in pregnancy of women with CHD.

OBJECTIVES: Pregnancy-related physiological adaptations result in increased heart rate as well as electrocardiographic changes such as a mean QTc prolongation of 27 ms. Pregnant women with CHD are at increased risk for cardiovascular complications. The aim of this study was to identify risk factors for abnormally prolonged QTc interval-a risk factor for ventricular arrhythmias-in pregnant women with CHD. MATERIAL AND METHOD: Retrospective longitudinal single-centre study. Pre-pregnancy demographic and electrocardiographic risk factors for abnormal QTc duration during pregnancy of (a) > 460 ms and (b) >27 ms increase were analyzed. RESULTS: Eighty-three pregnancies in 63 women were included, of which three had documented arrhythmias. All five Modified World Health Organization Classification of Maternal Cardiovascular Risk (mWHO) classes were represented, with 15 pregnancies (18.1%) in mWHO class I, 26 (31.3%) in mWHO II, 28 (33.7%) in mWHO II-III, 11 (13.3%) in mWHO III, and three pregnancies (3.6%) in mWHO class IV. Heart rate and QTc interval increased, while QRS duration and PR interval shortened during pregnancy. QTc duration of > 460 ms was associated with increased pre-pregnancy QTc interval, QRS duration, and weight, as well as body mass index. QTc increase of > 27 ms was associated with increased heart rate prior to pregnancy. No significant associations of electrocardiographic changes with mWHO class or CHD type were identified. CONCLUSION: Increased QTc in pregnant women with CHD was associated with being overweight or having higher heart rate, QRS, or QTc duration prior to pregnancy. These patients should be monitored closely for arrhythmias during pregnancy.

The effect of antipsychotic medications on QTc and delirium in paediatric cardiac patients with ICU delirium.

OBJECTIVE: Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation. DESIGN: Retrospective study, July 1, 2017-May 31, 2022. SETTING: Tertiary children's hospital. PATIENTS: Included were patients admitted to the paediatric cardiac ICU at Children's Healthcare of Atlanta. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65-32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5-7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002). CONCLUSIONS: The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.

Manual vs. automatic assessment of the QT-interval and corrected QT.

AIMS: Sudden cardiac death (SCD) is challenging to predict. Electrocardiogram (ECG)-derived heart rate-corrected QT-interval (QTc) is used for SCD-risk assessment. QTc is preferably determined manually, but vendor-provided automatic results from ECG recorders are convenient. Agreement between manual and automatic assessments is unclear for populations with aberrant QTc. We aimed to systematically assess pairwise agreement of automatic and manual QT-intervals and QTc. METHODS AND RESULTS: A multi-centre cohort enriching aberrant QTc comprised ECGs of healthy controls and long-QT syndrome (LQTS) patients. Manual QT-intervals and QTc were determined by the tangent and threshold methods and compared to automatically generated, vendor-provided values. We assessed agreement globally by intra-class correlation coefficients and pairwise by Bland-Altman analyses and 95% limits of agreement (LoA). Further, manual results were compared to a novel automatic QT-interval algorithm. ECGs of 1263 participants (720 LQTS patients; 543 controls) were available [median age 34 (inter-quartile range 35) years, 55% women]. Comparing cohort means, automatic and manual QT-intervals and QTc were similar. However, pairwise Bland-Altman-based agreement was highly discrepant. For QT-interval, LoAs spanned 95 (tangent) and 92 ms (threshold), respectively. For QTc, the spread was 108 and 105 ms, respectively. LQTS patients exhibited more pronounced differences. For automatic QTc results from 440-540 ms (tangent) and 430-530 ms (threshold), misassessment risk was highest. Novel automatic QT-interval algorithms may narrow this range. CONCLUSION: Pairwise vendor-provided automatic and manual QT-interval and QTc results can be highly discrepant. Novel automatic algorithms may improve agreement. Within the above ranges, automatic QT-interval and QTc results require manual confirmation, particularly if T-wave morphology is challenging.

Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes.

BACKGROUND: QT prolongation increases cardiovascular mortality in diabetes. The risk factors for QT prolongation vary across different studies. There is no data on the QT prolongation in patients with diabetes from the Arab region, where diabetes is highly prevalent. Here we aimed to assess the prevalence of QT prolongation and its associated risk factors in patients with type 2 diabetes from Saudi Arabia. METHOD: This was a retrospective, cross-sectional, hospital-based file review study. Data were collected from the medical records of patients with type 2 diabetes aged above 14 years and underwent ECG examination, and laboratory investigations were done within one month of ECG. RESULTS: The study included 782 patients with a prevalence of QTc prolongation of 13%. Patients with prolonged QTc interval were characterized by older age, higher BMI, longer diabetes duration, lower total cholesterol and LDL-C, and more diabetic nephropathy, hypertension, and CVD cases. They were also more in insulin treatment, antihypertensive medications, loop diuretics, and potassium-sparring diuretics. Logistic regression analysis revealed the odds of prolonged QTc interval increased significantly with CVD (OR = 1.761, 95% CI:1.021-3.036, p = 0.042), and usage of loop diuretics (OR = 2.245, 95% CI:1.023-4.923, p = 0.044) after adjusting for age, gender, and duration of diabetes. CONCLUSION: The risk factors associated with QTc prolongation in patients with type 2 diabetes are CVD, and loop diuretics. Age, BMI, and diabetes duration were more in people with QTc prolongation, whereas total cholesterol and LDL-C levels were lower. More patients had diabetic nephropathy, hypertension, and CVD with prolonged QTc.

The influence of different glucose tolerance on QTc interval: a population-based study.

BACKGROUND: Corrected QT (QTc) interval has been reported to be associated with type 2 diabetes. This study aimed to explore the relationship between different glucose tolerance and QTc intervals among middle-aged and older Chinese individuals. METHODS: We conducted a cross-sectional analysis that included 9898 subjects (3194 men and 6704 women) in a Chinese population. Glucose tolerance was studied during the oral glucose tolerance test (OGTT). Insulin, blood pressure, hemoglobin A1c (HbA1c), serum lipids, hepatic transaminases and waist-to-hip ratio were assessed. The QTc interval was derived from ECG recordings, and the subjects were stratified based on different glucose tolerance. RESULTS: QTc interval levels were increased significantly in the subjects with abnormal glucose metabolism compared with the normal glucose regulation group. Multiple regression analyses showed that the QTc interval was significantly associated with fasting plasma glucose, 2-h OGTT plasma glucose and HbA1c. The odds ratio of prolonged QTc was 1.396 for impaired glucose regulation (IFG)/impaired fasting glucose (IGT) (95% CI 0.126-1.730), and 1.342 for type 2 diabetes (95% CI 0.142-1.577) after all potential confounders were adjusted. CONCLUSIONS: Impaired glucose tolerance (IGR) and diabetes are associated with prolonged QTc intervals among middle-aged and older Chinese individuals. Abnormal glucose regulation can be used to monitor the QTc interval in the population.

The optimal QTc selection in patients of acute myocardial infarction with poor perioperative prognosis.

BACKGROUND: The predictive utility of QTc values, calculated through various correction formulas for the incidence of postoperative major adverse cardiovascular and cerebrovascular events (MACCE) in patients experiencing acute myocardial infarction (AMI), warrants further exploration. This study endeavors to ascertain the predictive accuracy of disparate QTc values for MACCE occurrences in patients with perioperative AMI. METHODS: A retrospective cohort of three hundred fourteen AMI patients, comprising 81 instances of in-hospital MACCE and 233 controls, was assembled, with comprehensive collection of baseline demographic and clinical data. QTc values were derived employing the correction formulas of Bazett, Fridericia, Hodges, Ashman, Framingham, Schlamowitz, Dmitrienko, Rautaharju, and Sarma. Analytical methods encompassed comparative statistics, Spearman correlation analysis, binary logistic regression models, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). RESULTS: QTc values were significantly elevated in the MACCE cohort compared to controls (P < 0.05). Spearman's correlation analysis between heart rate and QTc revealed a modest positive correlation for the Sarma formula (QTcBaz) (ρ = 0.46, P < 0.001). Within the multifactorial binary logistic regression, each QTc variant emerged as an independent risk factor for MACCE, with the Sarma formula-derived QTc (QTcSar) presenting the highest hazard ratio (OR = 1.025). ROC curve analysis identified QTcSar with a threshold of 446 ms as yielding the superior predictive capacity (AUC = 0.734), demonstrating a sensitivity of 60.5% and a specificity of 82.8%. DCA indicated positive net benefits for QTcSar at high-risk thresholds ranging from 0 to 0.66 and 0.71-0.96, with QTcBaz, prevalent in clinical settings, showing positive net benefits at thresholds extending to 0-0.99. CONCLUSION: For perioperative AMI patients, QTcSar proves more advantageous in monitoring QTc intervals compared to alternative QT correction formulas, offering enhanced predictive prowess for subsequent MACCE incidents.

Risk Stratification of QTc Prolongation in Critically Ill Patients Receiving Antipsychotics for the Management of Delirium Symptoms.

BACKGROUND: Patients experiencing significant agitation or perceptual disturbances related to delirium in an intensive care setting may benefit from short-term treatment with an antipsychotic medication. Some antipsychotic medications may prolong the QTc interval, which increases the risk of potentially fatal ventricular arrhythmias. In this targeted review, we describe the evidence regarding the relationships between antipsychotic medications and QTc prolongation and practical methods for monitoring the QTc interval and mitigating arrhythmia risk. METHODS: Searches of PubMed and Cochrane Library were performed to identify studies, published before February 2023, investigating the relationships between antipsychotic medications and QTc prolongation or arrhythmias. RESULTS: Most antipsychotic medications commonly used for the management of delirium symptoms (eg, intravenous haloperidol, olanzapine, quetiapine) cause a moderate degree of QTc prolongation. Among other antipsychotics, those most likely to cause QTc prolongation are iloperidone and ziprasidone, while aripiprazole and lurasidone appear to have minimal risk for QTc prolongation. Genetic vulnerabilities, female sex, older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications also increase the risk of QTc prolongation. For individuals at risk of QTc prolongation, it is essential to measure the QTc interval accurately and consistently and consider medication adjustments if needed. CONCLUSIONS: Antipsychotic medications are one of many risk factors for QTc prolongation. When managing agitation related to delirium, it is imperative to assess an individual patient's risk for QTc prolongation and to choose a medication and monitoring strategy commensurate to the risks. In intensive care settings, we recommend regular ECG monitoring, using a linear regression formula to correct for heart rate. If substantial QTc prolongation (eg, QTc > 500 msec) is present, a change in pharmacologic treatment can be considered, though a particular medication may still be warranted if the risks of discontinuation (eg, extreme agitation, removal of invasive monitoring devices) outweigh the risks of arrhythmias. AIMS: This review aims to summarize the current literature on relationships between antipsychotic medications and QTc prolongation and to make practical clinical recommendations towards the approach of antipsychotic medication use for the management of delirium-related agitation and perceptual disturbances in intensive care settings.

Dear Doctor Letters regarding citalopram and escitalopram: guidelines vs real-world data.

Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs' effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14-5% and 47-31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs' recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.

Abnormal blood lipid and electrocardiogram characteristics in common mental disorders.

BACKGROUND: At present, there is not enough evidence to prove the relationship between blood lipid and electrocardiogram (ECG) abnormalities in common mental disorders (CMD). This study aimed to explore the relationship between them, to detect and prevent arrhythmia or sudden death. METHODS: We collected 272 CMD patients (maintained a fixed drug dose pattern for 1 year or more), including 95 schizophrenias (SC), 90 bipolar disorders (BD) and 87 major depressive disorders (MDD), and 78 healthy controls (HC) from the Third People's Hospital of Foshan, China. We analyzed and compared their blood lipid and ECG indicators, to clarify the relationship between them. RESULTS: 350 participants were included. There were no significant differences in age, gender, total cholesterol (TC), low density lipoprotein (LDL) and QTc (p > 0.05) among subjects. And there were significant differences in body mass index (BMI), triglyceride (TG), high density lipoprotein (HDL), heart rate, PR interval and QRS width (p < 0.05). Person correlation analysis showed that QRS width was positively correlated with BMI and TG. And negatively correlated with HDL. Meanwhile, QTc was positively correlated with BMI. Multiple linear regional analysis further proved that TG (B = 3.849, p = 0.007) and LDL (B = 11.764, p = 0.018) were the risk factors, and HDL (B = -9.935, p = 0.025) was the protective factor for QRS width increase. CONCLUSION: Long term medication of CMD patients should strengthen weight management, and conduct regular blood lipid and ECG examinations to achieve early detection and intervention in order to promote their health.

Association between pre-operative prolonged corrected QT interval and all-cause mortality after non-cardiac surgery.

BACKGROUND: Prolonged corrected QT interval (QTc) has been linked to risk of arrhythmias and mortality in the general population. Pre-operative electrocardiography is often obtained for patient-and procedural cardiovascular risk assessment. The aim of this study was to investigate the association of pre-operative QTc and all-cause mortality in a non-cardiac surgical cohort. METHODS: A retrospective study of all patients over 18 years undergoing non-cardiac surgery at Landspitali-the National University Hospital in Iceland between 2 January 2005 to 31 December 2015, with follow-up through 20 May 2016. Patients were separated into five categories according to their pre-operative QTc interval ≤ 379, 380-439 (reference group), 440-479, 480-519 and ≥520 ms. Primary outcome was long-term mortality and secondary outcome was 30-day mortality. RESULTS: A total of 10,209 surgeries for 10,209 individuals were included. The median follow-up for mortality was 2691 days (interquartile range [IQR] 1620-3705 days). Patients with longer QTc interval had a higher comorbidity burden, were more likely to undergo emergency surgery and were often prescribed cardiac medications. After adjustment for confounding variables, the hazard ratio (HR) for long-term mortality compared with reference (QTc 380-439 ms) was 0.85 [CI: 0.66-1.09] for QTc ≤379, 1.08 [CI: 0.99-1.17] for QTc 440-479 ms, 1.26 [CI: 1.10-1.43] for QTc between 480 and 519 ms and 0.97 [CI: 0.78-1.21] for QTc ≥520 ms. When compared with reference, only patients with QTc interval between 480 and 519 ms had higher odds ratio for 30-day mortality as odds ratio for other groups were following; 1.12 [CI: 0.18-3.8] for ≤379 ms, 1.03 [CI: 0.70-1.51] for QTc 440-479 ms, 1.64 [CI: 1.02-2.60] for QTc 480-519 ms and 0.98 [0.44-2.06] for QTc ≥520 ms. CONCLUSION: Pre-operative QTc between 480 and 519 ms is associated with both higher long-term and 30-day mortality after non-cardiac surgery. The results suggest that this could reflect an underlying cardiovascular risk.

Dysrhythmias associated with COVID-19: Review and management considerations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is known to affect the cardiovascular system. Cardiac manifestations in COVID-19 can be due to direct damage to the myocardium and conduction system as well as by the disease's effect on the various organ systems. These manifestations include acute coronary syndrome, ST- segment elevations, cardiomyopathy, and dysrhythmias. Some of these dysrhythmias can be detrimental to the patient. Therefore, it is important for the emergency physician to be aware of the different arrhythmias associated with COVID-19 and how to manage them. This narrative review discusses the pathophysiology underlying the various arrhythmias associated with COVID-19 and their management considerations.

QTc prolongation during levofloxacin and triazole combination chemoprophylaxis: Prevalence and predisposing risk factors in a cohort of hematopoietic cell transplantation recipients.

BACKGROUND: QTc interval prolongation has been reported when combining fluoroquinolones and triazoles for chemoprophylaxis in cancer patients. Herein, we aimed to identify the prevalence and contributing factors to QTc prolongation in hematopoietic cell transplantation (HCT) recipients who received these agents during the neutropenic phase. METHODS: This is a retrospective medical chart review conducted at a university hospital in Lebanon from 2017 to 2020. It included all adult HCT inpatients on antimicrobial prophylaxis with fluoroquinolones and triazoles and whose baseline ECG monitoring done prior to chemoprophylaxis administration, then on day-3 and day-6 of therapy, were available. RESULTS: Overall, 68 HCT recipients met our inclusion criteria, of which 22% developed QTc prolongation. Based on bivariate analysis, female gender contributed to QTc prolongation (P = 0.001). There was a trend to QTc prolongation in patients with predisposing thyroid disease (P = 0.12), grade 2 vomiting and diarrhea (P = 0.16, P = 0.46, respectively), baseline hypokalemia (P = 0.18) and hypocalcemia (P = 0.3), hypomagnesemia on day-3 (P = 0.21) and day-6 hyponatremia (P = 0.36). Patients receiving two or more drugs with a known or probable risk of QTc prolongation (other than the fluoroquinolone/ triazole combination) were more prone to experience a prolonged QTc interval (P = 0.09). None of the patients that had QTc prolongation died or developed serious arrhythmias. CONCLUSION: The prevalence of QTc prolongation was 22% among HCT recipients on fluoroquinolone and triazole prophylaxis, yet we did not identify any independent risk factors for this issue. None of the patients that had QTc interval prolongation died or developed serious arrhythmias.