Corrected QT Research Articles

Pharmacological options for Candida albicans Endocarditis at the roadblock with irrecoverable prosthetics and drug interactions: a case report and review of literature

BackgroundCandidemia is the fourth most common nosocomial bloodstream infection. Endocarditis from candidemia is a rare but possibly fatal complication. The efficacy of amphotericin and echinocandins for induction and azoles for suppression has been well studied. Source control of infection, including removal of foreign bodies, remains the cornerstone for the success of any antifungal therapy.Case PresentationWe are describing a case of a 63-years old patient with multiple comorbidities who developed candidemia secondary to Candida albicans. The prospect of curing the fungemia was made difficult by prosthetic devices, including prosthetic heart valves, intracardiac defibrillator, and inferior vena filter, which could not be extracted due to poor cardiovascular status and higher postoperative mortality risk. Combination therapy with amphotericin and 5-Flucytosine (5FC) was used with the first recurrence. Suppression with fluconazole was contraindicated due to prolonged corrected QT (QTc) interval. Isavuconazole was employed for chronic lifelong suppression.ConclusionRetaining prosthetics in higher surgical risk patients presents us with unique clinical and pharmacological challenges regarding breakthrough infections, drug interaction, and side effects from prolonged suppressive therapies.

Teaching medical students the QT interval and its autonomous regulation in a practical ECG course in physiology

Background: The QT interval is a well established marker for ventricular repolarization. As the QT interval is inversely regulated with the heart rate, several correction formula are established to calculate corrected QT intervals (QT c ). In practical courses of physiology, medical students learn the correct measurement of the QT interval and its autonomous regulation. For this, students record and analyse ECGs under resting conditions and during/following a workout. However, little is known about teaching QT/QT c skills in students. In particular, it is not established whether untrained medical students can determine the length of the QT interval in rest and following an exercise with sufficient accuracy to allow discussion of its physiological regulation. Methods: A full cohort of 3rd year medical students (n=380) participated in a practical ECG course. In each course (20 students), ECGs of volunteers were recorded in small groups (2-4 students) under resting conditions and immediately following standardised physical exercise (squats and push-ups). Students calculated HR, QT intervals and QT c intervals using Bazett’s exponential correction. Automatically calculated QT intervals were retrieved from the ECG devices. Following the course, QT intervals of the same ECG passages were measured by experienced physiology teachers and expert clinical electrophysiologists. To compare effects of established QT c correction formulas, QT c was calculated for all retrieved intervals using Bazett, Framingham, Fridericia and Hodges. Data were analysed on the level of individual experiments and as pooled data of student groups. Results: In 117 experiments, students reported resting HRs of ~70 bpm and corresponding QT intervals of ~360 ms. Following exercise, students found an average increase of the HR by ~75% and a decrease of the QT interval by ~25%. Using pooled data sets of each course, the overall efficacy of the Bazett formula could well be demonstrated. Students HR data were highly concordant with the data generated by the automated ECG routines, the experienced physiologists and the clinical electrophysiologists. While average QT and QT c intervals were also comparable between the groups, the variance was substantially higher in students data than in the other groups, especially in the exercise ECGs. In the HR ranges generated in the course, QT correction by Fridericia and Framingham was more efficient than by Bazett and Hodges. Conclusions: Untrained students can determine QT intervals from ECGs recorded under resting conditions and following a workout with sufficient accuracy to demonstrate the autonomous regulation of this important (bio)marker on the level of individual data sets. Due to the high individual variance of the QT c , however, we recommend QT c correction based on data pooled within each student group to discuss the relevance of the QT correction formulas. The study was financed by institutional budget. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Incidence of Myocarditis Associated with Diphtheria, Tetanus, and Pertussis Vaccine: A Rare Case Series

AbstractMyocarditis induced by diphtheria–tetanus–pertussis (DTP) vaccination is extremely rare, accounting for only two cases thus far. Hence, to supplement knowledge regarding its pathogenesis and treatment, we reported two cases of myocarditis associated with DTP vaccination in adults.Two patients (a 40-year-old female and a 43-year-old male) presented with mild symptoms and were hemodynamically stable. In both patients, the DTP vaccination was given 4 and 6 days before admission. Both patients had prolonged corrected QT interval (QTc), poor left ventricular function, and high troponin levels at admission. However, numerous ST segment depression was only noted in the first case. Bacteriology and virology study results were negative for any pathogen. No atherosclerotic lesions were observed by coronary angiography. Cardiac magnetic resonance imaging was only performed in the second case, which confirmed the diagnosis of myocarditis. Initial therapy was administered with a beta-blocker, angiotensin-converting enzyme inhibitor, and intravenous methylprednisolone. Nonetheless, in the first case, rapid clinical deterioration and sudden cardiac death occur within 3 days of hospitalization. Learn from the first case, a high-dose intravenous immunoglobulin (IVIG) treatment was initiated in the second case, which resulted in an improvement in left ventricular function and clinical symptoms, as well as a significant reduction in QTc interval and troponin levels.Rapid diagnostic testing and early recognition of the fulminant course is mandatory, allowing clinicians to aggressively treat the patient with high-dose intravenous immune globulin, thus obtaining a better outcome.

Comparison of different QT correction methods for nonclinical safety assessment in ketamine-anesthetized Indian rhesus monkeys (Macaca mulatta)

Rhesus monkeys are a non-rodent species employed in the preclinical safety evaluation of pharmaceuticals and biologics. These nonhuman primate species have been increasingly used in biomedical research because of the similarity in their ionic mechanisms of repolarization with humans. Heart rate and QT interval are two primary endpoints in determining the pro-arrhythmic risk of drugs. As heart rate and QT interval have an inverse relationship, any change in heart rate causes a subsequent change in QT interval. This warrants for calculation of a corrected QT interval. This study aimed to identify an appropriate formula that best corrected QT for change in heart rate. We employed seven formulas based on source-species type, clinical relevance, and requirements of various international regulatory guidelines. Data showed that corrected QT interval values varied drastically for different correction formulas. Equations were compared on their slope values based on QTc versus RR plots. The rank order of the slope for different formulas was (closest to farthest from zero) QTcNAK, QTcHAS, QTcBZT, QTcFRD, QTcVDW, QTcHDG, and QTcFRM. QTcNAK emerged to be the best correcting formula in this study. It showed the least correlation with the RR interval (r = −0.01) and displayed no significant difference amongst the sexes. As there is no universally recognized formula for preclinical use, the authors recommend developing a best-case scenario model for specific study designs and individual organizations. The data from this research will be helpful in deciding an appropriate QT correction formula for the safety assessment of new pharmaceuticals and biologics.

Valor pronóstico del intervalo Tpeak-Tend en el desarrollo de arritmias ventriculares subagudas intrahospitalarias en el síndrome de tako-tsubo

Introduction and objectivesThe clinical value of electrocardiogram (ECG) repolarization parameters associated with ventricular arrhythmias (VAs) in tako-tsubo syndrome is still under debate. We aimed to evaluate ECG predictors of subacute VAs, defined as those occurring after the first 48hours from admission. MethodsThis single-center observational study enrolled patients admitted to the cardiology department between 2012 and 2018 with a confirmed diagnosis of tako-tsubo syndrome. Data collection included a 12-lead ECG on admission and at 48hours, continuous telemetry monitoring, blood testing, transthoracic echocardiography, and coronary angiography during hospitalization. VAs events were defined as: premature ventricular contractions ≥ 2000 within a 24-hour window of telemetry monitoring, ventricular fibrillation, sustained ventricular tachycardia (VT), polymorphic VT, and non-sustained VT. ResultsA total of 87 patients (age 72±12 years) were enrolled. During a median of 8 days of hospitalization, subacute VAs were documented in 22 patients (25%) after a median of 91hours from admission. Subacute VAs were associated with an increase in mortality during hospitalization (P=.030). The corrected global (mean of the 12-lead ECG values) Tpeak-Tend interval at 48hours from admission was an independent predictor of subacute VAs and was statistically superior to the standard corrected QT interval (Z test, P=.040). A cut-off of 108 msec for the corrected global Tpeak-Tend yielded a 71% sensitivity and 72% specificity for subacute VAs. ConclusionsIn patients with tako-tsubo syndrome, subacute VAs are associated with repolarization alterations that can be identified on conventional ECG using the Tpeak-Tend interval.

Baseline glycated hemoglobin and potassium level correlated with pretreatment QT-corrected interval among patients with diabetic drug-resistant tuberculosis.

Bedaquiline is a core drug with an optimized background regimen for treating drug-resistant tuberculosis (DR-TB) patients. One of the adverse effects of bedaquiline is QT-corrected (QTc) interval prolongation. TB patients with diabetes mellitus (DM) are more likely to develop QTc interval prolongation during TB treatment than those without DM. This study aimed to correlate baseline electrolyte levels (potassium, calcium, and magnesium), thyroid-stimulating hormone (TSH), body mass index (BMI), blood glucose, glycated hemoglobin (HbA1c), and pretreatment QTc interval among patients with diabetic DR TB who received regimens containing bedaquiline. It was a prospective study with a cross-sectional design. Blood samples, BMI, and electrocardiogram were collected at baseline before starting the regimen for DR-TB. Pearson correlation was used to correlate between baseline electrolyte level, TSH, BMI, complete blood count, blood glucose, HbA1c, and pretreatment QTc interval. Seventy-two DR-TB patients met the inclusion criteria, half with DM. The blood glucose and HbA1c were significantly higher in patients with DM. Pretreatment QTc interval was similar between the two groups. Levels of calcium, magnesium, TSH, blood glucose, and BMI were not correlated with pretreatment QTc interval. There was a correlation between baseline potassium and HbA1c levels with pretreatment QTc interval (P < 0.05; r = 0.357 and r = -0.376, respectively). Baseline potassium level correlates with the pretreatment QTc interval in those without DM. Baseline HbA1c and potassium levels correlate with pretreatment QTc interval among DR-TB patients with DM. Our study indicates the importance of monitoring HbA1c and potassium levels during DR-TB therapy containing bedaquiline for early detection of QTc prolongation.

Prevalence and Clinical Characteristics of Patients with Torsades de Pointes Complicating Acquired Atrioventricular Block.

Female gender, degree of QT prolongation, and genetic susceptibility are known risk factors for developing torsades de pointes (TdP) during high-grade atrioventricular block (HG-AVB). Our objective was to analyze the prevalence and clinical characteristics of patients presenting with TdP and AVB (TdP [+]) in comparison with non-TdP patients with AVB (TdP [-]). All the ECGs from patients prospectively admitted for AVB (2 to 1, HG, and complete) at the University Hospital of Nice were analyzed. Automated corrected QT (QTc), manual measurements of QT and JT intervals, and Tpeak-to-end were performed at the time of the most severe bradycardia. From September 2020 to November 2021, 100 patients were admitted for HG-AVB. Among them, 17 patients with TdP were identified (8 men; 81 ± 10 years). No differences could be identified concerning automated QTc, manual QTc (Bazett correction), baseline QRS width, or mean left ventricular ejection fraction between the two groups. Potassium serum level on admission and mean number of QT-prolonging drugs per patient were not significantly different between the two groups, respectively: 4.34 ± 0.5 mmol/L in TdP [+] versus 4.52 ± 0.6 mmol/L (p = 0.33); and 0.6 ± 0.7 in TdP [+] versus 0.3 ± 0.5 (p = 0.15). In contrast, manual QTcFR (Fridericia correction), JT (Fridericia correction), Tpeak-to-end, and Tpe/QT ratio were significantly increased in the TdP [+] group, respectively: 486 ± 70 ms versus 456 ± 53 ms (p = 0.04); 433 ± 98 ms versus 381 ± 80 ms (p = 0.02); 153 ± 57 ms versus 110 ± 40 ms (p < 0.001); and 0.27 ± 0.08 versus 0.22 ± 0.06 (p < 0.001). The incidence of TdP complicating acquired AVB was 17%. Longer QTcFR, JT, and Tpeak-to-end were significantly increased in the case of TdP but also in the presence of permanent AVB during the hospitalization.

QTc interval measurement in patients with right bundle branch block: A practical method.

Prolonging the QT interval in the right bundle branch block (RBBB) can create challenges for electrophysiologists in estimating repolarization time and eliminating the effect of depolarization changes on QT interval. In this study, we aimed to develop a practice formula to eliminate the effect of depolarization changes on QT interval in patients with RBBB. This prospective study evaluated accidentally induced RBBB in patients undergoing electrophysiological study. Two expert electrophysiologists recorded the ECG parameters, including QRS duration, QT interval, and cycle length, in the patients. The formula was developed based on QT interval differences (with and without RBBB) and its proportion to QRS. Additionally, the Bazzet, Rautaharju, and Hodge formulas were used to evaluate QTc. We evaluated 96 patients in this study. The mean QT interval without RBBB was 369.39 ± 37.38, reaching 404.22 ± 39.23 after inducing RBBB. ΔQT was calculated as 34.83 ± 17.61, and the ratio of ΔQT/QRS with RBBB was almost 23%. Our formula is: (QTwith RBBB - 23% × QRS). Subtraction of 25% instead of 23% seems more straightforward and practical. Our formula could also predict the QTc interval in RBBB based on the Bazzet, Rautaharju, and Hodge formulas. Previous formulas for QT correction were hard to apply in the clinical setting or were not specified for RBBB. Our new formula allows a rapid and practical method for QT correction in RBBB in clinical practice.

Prognostic significance of prolonged corrected QT interval in cerebral contusion.

Cerebral contusion (CC) results in a release of catecholamines, autonomic dysfunction and neural stimulation that can lead to a number of cardiac adverse events, so it is critical to determine these. So the objective of this study was to investigate the prognostic significance of electrocardiographic changes, particularly the effects of a prolonged corrected QT (QTc) interval in CC. In this retrospective cohort study, 110 patients with CC were evaluated. Age, sex, concomitant diseases, Glasgow Coma Scale on admission, radiological assessment of the contusion (location, size, course and presence of cerebral oedema), need for surgical intervention, length of hospital stay and the extended Glasgow Outcome Scale (GOS-E) were statistically analysed within the QTc interval by routine electrocardiography (ECG) on admission. The prolonged QTc interval was found to be associated with a higher incidence of cerebral oedema and a significantly higher risk of needing surgery. Patients with a prolonged QTc interval had a significantly larger contusion volume, greater midline shift and longer hospital stay, so their GOS-E score was significantly lower. A prolonged QTc interval on admission resulted in a hospital stay of more than eight days (sensitivity: 0.97 and specificity: 0.86), a higher risk of midline shift of more than 0.45 cm (P=0.006, sensitivity: 0.80 and specificity: 0.99) and a GOS-E score of <7 (sensitivity: 0.97 and specificity: 0.85). ECG changes on admission showing a prolonged QTc interval have prognostic significance in CC. This simple and easily applicable information should be taken into consideration at the time of clinical decision making which may prevent an adverse events survivor.

Analysis of Electrocardiogram Characteristics and its Influencing Factors in Thyroid Carcinoma

To investigate the characteristics and influencing factors of electrocardiogram changes in patients with thyroid cancer after operation. This study retrospectively analyzed the case data of 122 patients who underwent thyroid surgery for the first time in the department of breast and thyroid surgery from January 2020 to December 2021. All patients were pathologically confirmed to be papillary thyroid carcinoma. Firstly, the perioperative changes of electrocardiogram indexes were compared in all patients and then the influencing factors (age, sex, blood lipid level, body mass index and surgical method) of perioperative electrocardiogram changes were analyzed by univariate analysis. After operation, the serum thyroid stimulating hormone of all patients was higher and serum free triiodothyronine and free thyroxine were lower than that before operation (p<0.05). After operation, PR interval and QRS duration was shorter than before operation (p<0.05). The perioperative changes of heart rate were statistically significant in different age groups (p=0.043). The age group ≥55 y old had more obvious heart rate changes than the age group <55 y old. There was a difference in heart rate change between groups in different body mass index group (p=0.05). Perioperative free triiodothyronine was positively correlated with heart rate (r=0.476, p=0.004). The change of perioperative free thyroxine was negatively correlated with the change of PR interval duration (r=-0.411, p=0.016). The difference of perioperative corrected QT interval between male and female was statistically significant (p=0.027). There was a negative correlation between perioperative free thyroxine change and p wave change (r=-0.416, p=0.014). Age, gender and body mass index have a certain influence on the changes of perioperative electrocardiogram indicators. Postoperative cardiac function monitoring should be strengthened in elderly and obese patients. The change of thyroid hormone level is correlated with the change of perioperative electrocardiogram index. In the process of long-term thyroid stimulating hormone suppression treatment after operation, it can be tried to establish the sex-age related electrocardiogram standard of stratified thyroid hormone level.

Current updates on arrhythmia within Timothy syndrome: genetics, mechanisms and therapeutics.

Timothy syndrome (TS), characterised by multiple system malfunction especially the prolonged corrected QT interval and synchronised appearance of hand/foot syndactyly, is an extremely rare disease affecting early life with devastating arrhythmia. In this work, firstly, the various mutations in causative gene CACNA1C encoding cardiac L-type voltage-gated calcium channel (LTCC), regard with the genetic pathogeny and nomenclature of TS are reviewed. Secondly, the expression profile and function of CACNA1C gene encoding Cav1.2 proteins, and its gain-of-function mutation in TS leading to multiple organ disease phenotypes especially arrhythmia are discussed. More importantly, we focus on the altered molecular mechanism underlying arrhythmia in TS, and discuss about how LTCC malfunction in TS can cause disorganised calcium handling with excessive intracellular calcium and its triggered dysregulated excitation-transcription coupling. In addition, current therapeutics for TS cardiac phenotypes including LTCC blockers, beta-adrenergic blocking agents, sodium channel blocker, multichannel inhibitors and pacemakers are summarised. Eventually, the research strategy using patient-specific induced pluripotent stem cells is recommended as one of the promising future directions for developing therapeutic approaches. This review updates our understanding on the research progress and future avenues to study the genetics and molecular mechanism underlying the pathogenesis of devastating arrhythmia within TS, and provides novel insights for developing therapeutic measures.

Characterisation of the Cardiovascular Effects of a Meal: QTcF Assessment and Further Insights into the Physiological Effects

The electrical activity of the heart, characterised by the QT interval on an electrocardiogram (ECG), serves as a crucial parameter for evaluating cardiac health. Variations in the QT interval, particularly when corrected for heart rate using Fridericia's formula (QTcF), have long been of interest in cardiology and play a pivotal role in assessing cardiac safety in clinical trials. Understanding the influence of meals given at different times on QTcF intervals is essential for the accurate execution of Thorough QT (TQT) studies. Moreover, it has been proposed that this meal-related QT interval shortening could serve as a valuable indicator of assay sensitivity in TQT studies or even as a potential integration of TQT investigations into in Phase I/II studies. This study explores the impact of meals on QTcF intervals, specifically in the context of pharmacodynamic studies and TQT investigations. The primary goal is to gain insights into how different meals and baseline calculations affect QTcF changes and their potential implications for cardiac health and the risk of arrhythmias. Recent research has begun shedding light on the intricate relationship between meal composition, timing, and QTcF alterations. Several studies have investigated the effects of various nutrients, such as carbohydrates, fats, and proteins, on QTcF duration, as well as the implications of postprandial changes. These investigations have unveiled the complex interplay between dietary components and the cardiovascular system, raising essential questions about how our dietary choices may influence cardiac electrophysiology. In this comprehensive meta-analysis, we analyse data from nine studies, all conducted in accordance with Good Clinical Practice and ethical standards. These studies were approved by Ethics Committees and Regulatory authorities. Our analysis focuses on ECG assessments, involving the use of 12-lead ECGs recorded electronically and evaluated by certified cardiologists. We apply the Fridericia formula for QT correction (QTcF), as it has been shown to provide more accurate results across different heart rates compared to other correction methods. Our findings confirm existing literature into the impact of meals on QTcF intervals. We observe a consistent shortening of QTcF following breakfast, exceeding 5 milliseconds, which aligns with the positive control requirement defined by ICH E14, thus demonstrating the validity of our approach. In contrast, the effect of lunch is consistently less than 5 milliseconds across various timepoints and studies, indicating differences in the meal-related QTcF changes. Furthermore, our analysis incorporates gender-based assessments, showing that women exhibit a smaller effect than men, which is significant for breakfast and the fasted condition. These results suggest that the observed QTcF effect post-breakfast is a combination of the meal itself and factors unique to the initial day of a study. This insight holds potential for improving the design and interpretation of cardiac safety studies, particularly in Phase I investigations, and may offer the opportunity to explore the removal of positive control agents like Moxifloxacin, thereby reducing exposure to harmful challenge agents and contributing to the global effort to combat antimicrobial resistance (AMR). In conclusion, this meta-analysis advances our understanding of meal-induced QTcF changes and their significance in cardiac safety assessment, offering the prospect of more efficient and patient-focused drug development practices. This not only contributes to enhanced safety but also supports the reduction of antibiotic consumption, a key element in the global fight against AMR.

Adolescent Drug Ingestions Requiring ICU Stay: Single-Center Retrospective Cohort Study.

Ingestions are a prevalent form of self-harm in teenagers and are unfortunately an increasingly common reason for admission to both acute care and critical care services. The goal of this study was to identify characteristics associated with requiring PICU stay among adolescents hospitalized for ingestions. Retrospective cohort study comparing patients admitted to hospital medicine service and critical care service from January 2019 to December 2019. Freestanding children's hospital in the midwestern United States. Adolescents 12-18 years old hospitalized for ingestion. None. Out of 209 patients included in the study cohort, 95 required PICU admission. High-risk behaviors (having had sex or usage of alcohol, drugs, tobacco, or vaping) were endorsed by 190 of 209 patients (91%). We compared patient characteristics, ingestion history, workup, and pharmacological and PICU-specific interventions between patients hospitalized on the hospital medicine service and the PICU. We failed to identify an association between reason for ingestion, substance ingested, and previously identified suicide risk factors including previous suicide attempt, previous self-harm, and psychiatric comorbidity and admission to PICU, as opposed to non-PICU admission. PICU stay was associated with longer peak corrected QT interval value, receiving a pharmacological intervention, and longer duration of hospital stay. Fifteen of 95 patients (16% [95% CI, 9-25%]) in the PICU received a PICU-specific intervention. We failed to identify specific patient demographics or mental behavioral health characteristics associated with PICU stay after ingestion. Therefore, we believe that all adolescents hospitalized due to ingestion-irrespective of disposition-should receive standardized high-risk behavior screening due to the pervasive nature of these behaviors among this patient population. PICU-specific care, beyond observation, could be needed in as high as one-in-four PICU admissions. Further research is needed to inform optimal disposition and resource allocation for this patient population.

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

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. 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. 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. 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.

Cardiovascular risk factors and metabolic syndrome in patients treated with long-acting injectables antipsychotics: a retrospective study.

The present cross-sectional, retrospective study aimed to assess the prevalence of cardiovascular disease (CVD) risk factors and metabolic syndrome in a sample of psychiatric patients treated with long-acting injectable antipsychotics (LAIs). The clinical charts of 120 patients, mainly diagnosed with schizophrenia (30.0%), schizoaffective disorder (15.0%), and bipolar disorder (13.3%) on LAIs therapy - initiated in the period from 2013 to 2019 and lasting at least one year - were retrospectively reviewed and related socio-demographic, clinical and laboratory variables were collected. The 70.8% of patients were treated with first-generation LAIs, and the remaining 29.2% with second-generation LAIs. The overall sample showed low compliance in performing the required exams and evaluations related to CVD risk factors. The prevalence of metabolic syndrome was 30.8%, and, considering specific CVD risk factors, 55% of the total sample reported abdominal obesity, 43.3% arterial hypertension, 41.7% low HDL-cholesterol, 25.8% hypertriglyceridemia, and 20.8% fasting hyperglycemia. Lastly, 6.7% showed prolonged corrected QT (QTc) interval at the ECG. Patients treated with LAIs should be regularly monitored for metabolic changes and CVD risk factors. Metabolic changes rapidly develop after initiating an antipsychotic therapy and these often involve parameters, that can be easily recorded in an outpatient setting (e.g. abdominal obesity and hypertension).

352 PROGNOSTIC VALUE OF THE TPEAK-TEND INTERVAL FOR IN-HOSPITAL SUBACUTE VENTRICULAR ARRHYTHMIAS IN TAKOTSUBO SYNDROME

Abstract Introduction and objectives The clinical value of ECG repolarization parameters associated with ventricular arrhythmias (VAs) in Takotsubo syndrome is still under debate. We aimed to evaluate ECG predictors of subacute VAs, defined as those occurring after the first 48 hours from admission. Methods This is a single-center observational study enrolling patients admitted to the Cardiology Department between 2012 and 2018 with confirmed diagnosis of Takotsubo syndrome. Data collection included a 12-lead ECG on admission and at 48 hours, continuous telemetry monitoring, blood testing, transthoracic echocardiography and coronary angiography during hospitalization. VAs events were defined as: premature ventricular contractions ≥2000 within a 24-hour window of telemetry monitoring, ventricular fibrillation, sustained ventricular tachycardia (VT), polymorphic VT and non-sustained VT. Results A total of 87 patients (age 72±12 years old) were enrolled. During an average of 16±14 days of hospitalization, subacute VAs were documented in 22 patients (25%) after 127±75 hours from admission. Subacute VAs were associated with an increased in-hospital mortality (p=0.030). The corrected global (mean of the 12-lead ECG values) Tpeak-Tend interval at 48 hours from admission was an independent predictor of subacute VAs. The corrected global Tpeak-Tend was statistically superior to the standard corrected QT interval to predict subacute VAs (Z test, p=0.040). A cut-off of 108 msec for the corrected global Tpeak-Tend yielded a 71% sensitivity and 72% specificity for subacute VAs. Conclusions In patients with Takotsubo syndrome subacute VAs are associated with repolarization alterations that can be identified on the conventional ECG using the Tpeak-Tend interval.

Prognostic value of the Tpeak-Tend interval for in-hospital subacute ventricular arrhythmias in tako-tsubo syndrome

Introduction and objectivesThe clinical value of electrocardiogram (ECG) repolarization parameters associated with ventricular arrhythmias (VAs) in tako-tsubo syndrome is still under debate. We aimed to evaluate ECG predictors of subacute VAs, defined as those occurring after the first 48hours from admission. MethodsThis single-center observational study enrolled patients admitted to the cardiology department between 2012 and 2018 with a confirmed diagnosis of tako-tsubo syndrome. Data collection included a 12-lead ECG on admission and at 48hours, continuous telemetry monitoring, blood testing, transthoracic echocardiography, and coronary angiography during hospitalization. VAs events were defined as: premature ventricular contractions ≥ 2000 within a 24-hour window of telemetry monitoring, ventricular fibrillation, sustained ventricular tachycardia (VT), polymorphic VT, and non-sustained VT. ResultsA total of 87 patients (age 72±12 years) were enrolled. During a median of 8 days of hospitalization, subacute VAs were documented in 22 patients (25%) after a median of 91hours from admission. Subacute VAs were associated with an increase in mortality during hospitalization (P=.030). The corrected global (mean of the 12-lead ECG values) Tpeak-Tend interval at 48hours from admission was an independent predictor of subacute VAs and was statistically superior to the standard corrected QT interval (Z test, P=.040). A cut-off of 108 msec for the corrected global Tpeak-Tend yielded a 71% sensitivity and 72% specificity for subacute VAs. ConclusionsIn patients with tako-tsubo syndrome, subacute VAs are associated with repolarization alterations that can be identified on conventional ECG using the Tpeak-Tend interval.

Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The combination between medetomidine, midazolam, and butorphanol (MMB) is commonly used in different animal models. The possibility of MMB combination to establish the MI model in rats did not study yet which is difficult because of severe respiratory depression and delayed recovery post-surgery, resulting in significant deaths. Atipamezole is used to counter the cardiopulmonary suppressive effect of MMB. The aim of the present study is to establish MI model in rats using a novel anesthetic combination between MMB and Atipamezole. Twenty-five Sprague Dawley (SD) rats were included. Rats were prepared for induction of the Myocardial infarction (MI) model through thoracotomy. Anesthesia was initially induced with a mixture of MMB (0.3/5.0/5.0 mg/kg/SC), respectively. After endotracheal intubation, rats were maintained with isoflurane 1% which gradually reduced after chest closing. MI was induced through the left anterior descending (LAD) artery ligation technique. Atipamezole was administered after finishing all surgical procedures at a dose rate of 1.0 mg/kg/SC. Cardiac function parameters were evaluated using ECG (before and after atipamezole administration) and transthoracic echocardiography (before and 1 month after MI induction) to confirm the successful model. The induction time, operation time, and recovery time were calculated. The success rate of the MI model was also calculated. MI was successfully established with the mentioned anesthetic protocol through the LAD ligation technique and confirmed through changes in ECG and echocardiographic parameters after MI. ECG data was improved after atipamezole administration through a significant increase in heart rate (HR), PR Interval, QRS Interval, and QT correction (QTc) and a significant reduction in RR Interval. Atipamezole enables rats to recover voluntary respiratory movement (VRM), wakefulness, movement, and posture within a very short time after administration. Echocardiographic ally, MI rats showed a significant decrease in the left ventricular wall thickness, EF, FS, and increased left ventricular diastolic and systolic internal diameter. In addition, induction time (3.440 ± 1.044), operation time (29.40 ± 3.663), partial recovery time (10.84 ± 3.313), and complete recovery time (12.36 ± 4.847) were relatively short. Moreover, the success rate of the anesthetic protocol was 100%, and all rats were maintained for 1 month after surgery with a survival rate of 88%. Our protocol produced a more easy anesthetic effect and time-saving procedures with a highly successful rate in MI rats. Subcutaneous injection of Atipamezole efficiently counters the cardiopulmonary side effect of MMB which is necessary for rapid recovery and subsequently enhancing the survival rate during the creation of the MI model in rats.

Development of an AI-Driven QT Correction Algorithm for Patients in Atrial Fibrillation

BackgroundProlongation of the QTc interval is associated with the risk of torsades de pointes. Determination of the QTc interval is therefore of critical importance. There is no reliable method for measuring or correcting the QT interval in atrial fibrillation (AF). ObjectivesThe authors sought to evaluate the use of a convolutional neural network (CNN) applied to AF electrocardiograms (ECGs) for accurately estimating the QTc interval and ruling out prolongation of the QTc interval. MethodsThe authors identified patients with a 12-lead ECG in AF within 10 days of a sinus ECG, with similar (±10 ms) QRS durations, between October 23, 2001, and November 5, 2021. A multilayered deep CNN was implemented in TensorFlow 2.5 (Google) to predict the MUSE (GE Healthcare) software-generated sinus QTc value from an AF ECG waveform, demographic characteristics, and software-generated features. ResultsThe study identified 6,432 patients (44% female) with an average age of 71 years. The CNN predicted sinus QTc values with a mean absolute error of 22.2 ms and root mean squared error of 30.6 ms, similar to the intrinsic variability of the sinus QTc interval. Approximately 84% and 97% of the model’s predictions were contained within 1 SD (±30.6 ms) and 2 SD (±61.2 ms) from the sinus QTc interval. The model outperformed the AFQTc method, exhibiting narrower error ranges (mean absolute error comparison P < 0.0001). The model performed best for ruling out QTc prolongation (negative predictive value 0.82 male, 0.92 female; specificity 0.92 male, 0.97 female). ConclusionsA CNN model applied to AF ECGs accurately predicted the sinus QTc interval, outperforming current alternatives and exhibiting a high negative predictive value.

Accurate QT correction method from transfer entropy

The QT interval in the electrocardiogram (ECG) is a fundamental risk measure for arrhythmic adverse cardiac events. However, the QT interval depends on the heart rate and must be corrected accordingly. The present QT correction (QTc) methods are either simple models leading to under- or overcorrection, or impractical in requiring long-term empirical data. In general, there is no consensus on the best QTc method. We introduce a model-free QTc method-AccuQT-that computes QTc by minimizing the information transfer from R-R to QT intervals. The objective is to establish and validate a QTc method that provides superior stability and reliability without models or empirical data. We tested AccuQT against the most commonly used QT correction methods by using long-term ECG recordings of more than 200 healthy subjects from PhysioNet and THEW databases. AccuQT overperforms the previously reported correction methods: the proportion of false-positives is reduced from 16% (Bazett) to 3% (AccuQT) for the PhysioNet data. In particular, the QTc variance is significantly reduced and thus the RR-QT stability is increased. AccuQT has significant potential to become the QTc method of choice in clinical studies and drug development. The method can be implemented in any device recording R-R and QT intervals.