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Drug-induced prolongation of the QT interval is common in a variety of pharmaceutical treatments and can lead to serious clinical outcomes. Although substantial efforts have been made to prevent drug-induced QT interval prolongation, the lack of a centralized data source remains the main obstacle to further study of the underlying mechanism and the development of effective prediction strategies. To fill this gap, we propose a schema for stratifying the risk of marketed QT prolonging drugs based on US Food and Drug Administration (FDA)-approved drug labeling and developed a Drug-Induced QT Prolongation Atlas (DIQTA). Potential application of DIQTA was shown by precision dosing in off-label use and therapeutic strategy optimization, as well as the facilitation of artificial intelligence (AI)-based modeling in predictive toxicity.

Background: QTc prolongation is common in dangerous clinical conditions, associated with an increased risk of life-threatening arrhythmia torsades de pointes. The goal of this short communication is to evaluate the principal causes of risk of QTc prolongation that are observed in an emergency department and discuss the differences between drug- and non-drug-associated factors. Methods: The retrospective analysis was carried out on 130 patients that presented a QTc prolongation (>480 ms for man and >470 for female, respectively), admitted to the emergency department of a single Italian hospital. Patients with pace-maker (22) were excluded from this study. For each patient, a minimum of 3 ECGs (12 leads) were recorded. Attention was paid on electrolytes disturbances and to the pharmacotherapy, with a particular emphasis to the use of antibiotics. Results: Mean age of the patients was 79.6 years (SD=11.3) and females and males were almost equally present (46.6% F, 53.7% M). The average QTc value was 492.2 ms (493.3 ms F, 492.8 M). The patients were divided in those with electrolytes disturbances (24.0%), antimicrobial therapy (35.2%), both antimicrobial therapy and electrolytes disturbances (24.1%), and other causes of QTc prolongation (16.7%). Conclusion: This analysis shows the relevance of the empirical therapy established at the admission, in particular for infective diseases, as an important risk factor for the prolongation of QTc. Other factors that can increase the risk are electrolytes alterations, advanced age, cardiovascular diseases, and drug-drug interaction.

PR prolongation (first-degree AV block) is defined primarily as delayed conduction through the atrioventricular (AV) node, but can also signify delayed electrical impulse propagation through any part of the specialized conduction system. The prevalence of PR prolongation ranges from 1-5% in patients younger than 50 years of age, with increasing prevalence, particularly after the sixth decade of life and in patients with organic heart disease. While classical studies suggest no adverse associations linked to PR prolongation, contemporary studies have documented increased risk of atrial arrhythmias, heart failure, and mortality in patients with PR prolongation. Future studies are needed to risk stratify elderly patients with PR prolongation who may be at increased risk of adverse outcomes and determine the optimal monitoring strategy for future follow-up.

Prolongation of the QTc interval is associated with an increased risk of malignant ventricular dysrhythmias, such as ventricular tachycardia (VT), and sudden cardiac death. The quantifiable risk rates of adverse dysrhythmic outcome in relation to specific QTc interval length are not known. We conducted a literature review on the topic of QT interval prolongation in adult patients and the associated risk of malignant dysrhythmic event. We specifically formulated our literature search and subsequent literature review to address the following question: Can the clinician identify specific QTc intervals at which a specific quantifiable risk of malignant dysrhythmic event (malignant ventricular dysrhythmia and/or cardiac arrest) occurs in an undifferentiated adult patient population? In the literature search, we identified 701 studies; upon review using specific, pre-determined inclusion criteria, we identified 16 articles for inclusion in the review. From this literature, we were unable to answer the question in a quantifiable manner and only noted that the risk of malignant dysrhythmic event increases with progressively longer QTc interval. The current literature on this topic is inadequate to answer this important question due to heterogenous study methodology, patient populations, endpoints, and periods of observation. Additional prospective research is required on this topic, aimed at addressing the important issue of specific, quantifiable risk and its relation to degree of prolongation of the QTc interval.

Background: Azithromycin maintenance therapy is widely used in cystic fibrosis (CF), but little is known about its long-term safety. We investigated whether chronic azithromycin use is safe regarding renal function, hepatic cell toxicity and QTc-interval prolongation. Methods: Adult CF patients (72 patients using azithromycin for a cumulative period of 364.8 years and 19 controls, 108.8 years) from two CF-centers in the Netherlands with azithromycin (non)-use for at least three uninterrupted years were studied retrospectively. Results: There was no difference in mean decline of estimated glomerular filtration rate (eGFR), nor in occurrence of eGFR-events. No drug-induced liver injury could be attributed to azithromycin. Of the 39 azithromycin users of whom an ECG was available, 4/39 (10.3%) had borderline and 4/39 (10.3%) prolonged QTc-intervals, with 7/8 patients using other QTc-prolonging medication. Of the control patients 1/6 (16.7%) had a borderline QTc-interval, without using other QTc-prolonging medication. No cardiac arrhythmias were observed. Conclusion: We observed no renal or hepatic toxicity, nor cardiac arrythmias during azithromycin use in CF patients for a mean study duration of more than 5 years. One should be aware of possible QTc-interval prolongation, in particular in patients using other QTc-interval prolonging medication.

We aimed to define the prewarning sign of brainstem auditory evoked potentials (BAEPs) associated with cerebellar retraction (CR) during microvascular decompression surgery for hemifacial spasm.A total of 241 patients with a latency prolongation of 1 ms or an amplitude decrement of 50% of wave V were analyzed. According to BAEPs before significant changes during CR, patients were classified into Groups A (latency prolongation of wave I [≥0.5 ms] without prolongation of the I-III interpeak interval [0.5 ms]) and B (no latency prolongation of wave I [0.5 ms] with prolongation of the I-III interpeak interval [≥0.5 ms]). BAEPs and postoperative hearing loss (HL) were compared between the two groups.Group B comprised 160 (66.4%) patients. With maximal changes in wave V, latency prolongation (≥1 ms) with amplitude decrement (≥50%) was more common in Group B (p 0.018). At the end of the operation, wave V loss was observed in 11 patients, including 10 patients from Group B. Five patients developed postoperative HL; all were from Group B.Latency prolongation of wave III during CR was associated with serious BAEPs changes and postoperative HL.Latency prolongation of wave III is a significant prewarning sign.

QT Interval prolongation is common in insulin resistance state obesity. Insulin-induced hyperpolarization might be involved in ventricular repolarization leading to QTc lengthening. Therefore, this study is designated to investigate the relationship between corrected QT interval (QTc) prolongation and insulin resistance in obese adult male subjects. Apparently healthy adult male subjects (n=100) aged between 18-35 years residing in Magway Township were recruited by simple random sampling method. Then all the eligible subjects were categorized into 2 groups: non-obese [body mass index (BMI) 18.5 to 24.9 kg/m2, n= 40] and obese group [BMI ≥ 30.0 kg/m2, n=60] by their anthropometric parameters. Serum fasting glucose was measured by glucose oxidase method. Serum insulin level was determined by Enzyme-Linked Immunosorbent Assay (ELISA). Insulin sensitivity was calculated by Homeostatic Model Assessment (HOMA-IR). The QT interval was measured by routine 12-lead ECG and corrected QT interval (QTc) was calculated according to Bazett’s formula. In the present study, insulin sensitivity (HOMA-IR) was higher in obese subjects (4.64±2.3) than that of non-obese subjects (2.5±0.89) (p< 0.001). There was significant positive correlation between QTc and HOMA-IR (r = 0.41, p< 0.001, n = 100) in this study. HOMA-IR >3.8 was considered as insulin resistance (IR) and QTc > 440ms was regarded as QTc interval prolongation. Insulin resistance was significantly associated with prolonged QTc interval in the study population (X2=7.3, p< 0.05, n=100). Risk of QTc interval prolongation was 3.4 times higher in subjects with IR (Odd ratio = 3.4; 95% confidence interval = 1.37 to 8.45). It was concluded that prolonged QTc interval is associated with insulin resistance state.

QTc interval prolongation is common in patients with liver cirrhosis. Cirrhotic patients suffering from complications could also prolong QT interval. We aimed to explore the role of QTc interval prolongation in cirrhotic patients with upper gastrointestinal bleeding (UGIB). Overall, 167 patients were analyzed. QTc interval prolongation presented in 111 patients (66.5%). One hundred and seven patients (64.1%) suffered from acute UGIB. Results showed that RBC, Hb, ALB and calcium (Ca) were significantly lower, and DBIL, GGT, APTT, Child-Pugh score, MELD score and ALBI score were significantly higher in the prolongation group than those without QTc prolongation. AUROC of QTc was .699 (95%CI: .623-.768). In the acute UGIB subgroup, AUROC of QTc was .478 (95%CI: .347-.611). In the HBV subgroup, AUROC of QTc was .722 (95%CI: .616-.812). QTc interval prolongation was prevalent in cirrhotic patients with UGIB and correlated with liver dysfunction. QTc might not be a valid predictor of in-hospital mortality.

Many drug therapies are associated with prolongation of the QT interval. This may increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia. As the QT interval varies with a change in heart rate, various formulae can adjust for this, producing a ‘corrected QT’ (QTc) value. Normal QTc intervals are typically 65 years, uncorrected electrolyte disturbances); the potential risk and degree of QT prolongation associated with the proposed drug; and co-prescribed medicines that could increase the risk of QT prolongation. To support clinicians, who are likely to prescribe such medicines in their daily practice, we developed a simple algorithm to help guide clinical management in patients who are at risk of QT prolongation/TdP, those exposed to QT-prolonging medication or have QT prolongation.

Objective To summarize the proposed mechanisms behind hypertension and QT interval prolongation associated with use of targeted systemic cancer therapies and provide recommendations for monitoring or managing these toxicities. Summary The cardiotoxic effects of targeted systemic cancer therapies represents a new paradigm of cancer treatment associated cardiovascular adverse events. National guidelines regarding optimal monitoring and management strategies for hypertension and QT interval prolongation associated with use of these therapies are lacking. While the pathophysiological drivers of hypertension due to targeted systemic cancer therapies differ by class of targeted therapy, general management strategies do not. Routine blood pressure monitoring throughout the duration of therapy is recommended for all agents. Patients who experience hypertension often can be treated with the addition or modification of antihypertensive therapies. Uncontrolled hypertension despite optimal medical management may require dose modifications or discontinuation of the targeted systemic cancer therapy. Electrocardiogram monitoring is recommended for patients who receive targeted therapies that may prolong the QT interval. Minimizing or managing drug interactions with other QT prolonging medications is recommended in addition to ensuring adequate electrolyte supplementation. Dose modifications or discontinuation of the targeted systemic therapy may be necessary for patients who experience QT interval prolongation. Conclusions Appropriate cardiovascular monitoring and timely management of treatment-emergent toxicities can optimize therapy for patients receiving targeted systemic cancer therapies associated with a risk of drug-induced hypertension or QT interval prolongation.

Background The corrected QT (QTc) interval is a strong predictor of ischaemic heart disease and cardiovascular mortality. It may trigger lethal arrhythmias and sudden death. Risk factors include electrolyte disorders, medications, prior cardiovascular disease and genetic predisposition. We previously demonstrated that QTc intervals are prolonged in patients hospitalised with pneumonia, regardless which antibiotics were given. It is unclear whether QTc prolongation is associated with pneumonia itself or whether it occurs with other infections. Aims To investigate any association between hospitalisation for infection and QTc prolongation. Methods We enrolled 169 patients, 160 of whom were used for analysis. QTc was measured in seconds by routine electrocardiogram (ECG) on admission. Subsequently, daily ECG were performed for 3 days, or until discharge (whichever occurred sooner). When clinically significant QTc prolongation was detected, possible causes were investigated. Results Clinically significant prolongation was not observed in any patient. The QTc was slightly longer in patients hospitalised for pneumonia or upper respiratory tract infections on admission. It was also prolonged in men, in patients with ischaemic heart disease, hypertension, history of cerebrovascular accident or cancer. A very slight trend for prolongation was observed between the first and second day of monitoring, however it later returned to baseline levels. Nearly 54% of study participants had positive systemic inflammatory response syndrome scores, however no association was detected between their score and baseline QTc, or any subsequent prolongation. Conclusions We found no association between hospitalisation due to infection and prolongation of the QTc interval.

Infective endocarditis (IE) is a serious medical condition with a high morbidity and mortality rate. Staphylococcus aureus is the most common etiologic organism in IE. While echocardiography plays an important role in diagnosis and management of IE, the electrocardiogram (ECG) is helpful in determination of disease progression as well as in prognostication. We present a case of a 72-year-old man who was diagnosed with IE following methicillin resistant Staphylococcus aureus (MRSA) bacteremia. The course of hospitalization was complicated with multiple septic-embolic strokes and aortic root abscess. Serial ECG revealed PR prolongation and new onset left bundle branch block (LBBB) before the patient became terminal. Our case highlights the utility of serial ECGs monitoring in the patients with IE that may reveal subtle ECG findings, such as PR prolongation and LBBB. These findings which might serve as a clue of the presence of peri-annular extension of IE, help in prognostication and aid in the therapeutic decision-making such as early surgical intervention in these high-risk patients with poor prognosis. In this report, we also present the pathophysiologic mechanisms underlining the ECG changes in patients with aortic valve endocarditis.

Background: Based on previous studies, vitamin D deficiency could lead to nerve stimulation. The purpose of the present study was to determine frequency and duration of seizures in children with idiopathic epilepsy in two groups; normal level of vitamin D versus decreased level of vitamin D. Methods: This pilot, comparative study was carried out in Zanjan University of Medical Sciences on total 40 children aging between 2 to 12 years old (23 male and 17 female) with the diagnosis of idiopathic epilepsy. All patients were receiving anti-epileptic drugs. The initial questionnaire was completed by each parent. Total 40 epileptic cases were examined in close follow-ups every three months, during total 9 months. Meanwhile, the frequency and duration of each seizure were recorded in questionnaire at every three-month period. Vitamin D blood samples were analyzed at the beginning of the study and after 9 months following the study. Serum levels of Vitamin D were analyzed by ELISA method (Elecsys2010, RocheCo, Germany; STAR FAX; 2100), simultaneously, Vitamin D level Results: In all 40 patients, vitamin D level less than 30 ng/ml was detected in 32% (13 patients) at the beginning of study and 35% (14 patients) in 9 months later (13 patients were common between the two groups). There was no significant relationship between the frequency of seizures, the duration of seizures and vitamin D levels in patients. The relationship between positive family history of epilepsy and the number of seizures was reported significant. The frequency of vitamin D deficiency was higher in female cases in final evaluation. Conclusion: In the present study, a considerable correlation was detected between the frequency of seizures and positive history of seizure in the family. The frequency of vitamin D deficiency was higher in female cases in final analysis. No significant relationship was detected between the number of seizures, the mean duration of seizures and serum level of Vitamin D in children who received anticonvulsant drugs. However, vitamin D deficiency in patients was not overlooked in order to prevent known complications. We recommend a randomized clinical trial in the future with an adequate sample size. Moreover, a non-epileptic control group in study would be useful.

The classical form of typical Atrio Ventricular Node Reentrant Tachycardia (AVNRT) is a "slow-fast" pathways tachycardia and the usual therapy is an ablation of the slow pathway since it carries a low risk of AV block. In patients with long PR interval and/or living on the anterograde slow pathway an alternative technique is required. We report a case of a 42-year-old lady with idiopathic restrictive cardiomyopathy, persistent atrial fibrillation status post pulmonary vein isolation (PVI) and PVC ablation with a systolic dysfunction, who presented with incessant slow narrow complex tachycardia of 110 bpm that appeared to be an AVNRT. Her baseline EKG revealed a first-degree AV block with a PR of 320 ms. EP study showed no evidence of anterograde fast pathway conduction. Given this fact, the decision was to attempt an ablation of the retrograde fast pathway. The fast pathway was mapped during tachycardia to its usual location into the anteroseptal region, then radiofrequency (RF) ablation in this location terminated tachycardia. After ablation, she continued to have her usual anterograde conduction through slow pathway and the tachycardia became uninducible. In special populations with prolonged PR interval or poor anterograde fast pathway conduction, fast pathway ablation is the required ablation for typical AVNRT. This article is protected by copyright. All rights reserved.

Abnormal values for standard laboratory tests of coagulation are frequently reported in critically ill patients. Sepsis-associated coagulopathy with prolonged prothrombin time and thrombocytopenia is common among patients hospitalized in the intensive care unit (ICU). Isolated prolongation of activated partial thromboplastin time (aPTT) occurs less frequently in the ICU setting and has numerous causes. Moreover, there are several preanalytical factors that may impact on results obtained. Isolated prolongation of aPTT in the absence of clinically relevant bleeding is a common finding in patients in the ICU. The first step in the diagnostic process is exclusion of preanalytical error. Next, based on the clinical picture (normal haemostasis vs. bleeding tendency), the appropriate tests should be ordered, taking into account acquired and congenital causes. To establish a diagnosis in a timely fashion, the proposed practical diagnostic algorithm can be followed.

The assessment of the QT interval has been an integral part of ECG interpretation since the first descriptions of long QT syndrome by Wolff in 1950 and by Jervell and Lange-Nielsen in 1957. The correct measurement of the QT interval as well as a correct interpretation of the causes and of the clinical consequences of a QT prolongation, however, may be difficult even for trained internists and cardiologists. In this review, we give an overview on physiological determinants of cardiac repolarization, its marker in the surface ECG – the QT interval –, methods to correctly assess QT interval duration, causes for pathologically prolonged QT intervals, and resulting clinical consequences. A correct measurement of the QT interval should be performed by using the „tangent method“, excluding possible U waves. A heart rate correction formula should be employed to determine the heart rate corrected QT interval (QTc).Many factors, which may prolong the QT interval, should be checked whenever a QTc prolongation is observed. These include drugs, electrolyte imbalances, hormonal influence, and comorbidities. The correct management of a patient with (genetically determined) LQTS starts with a risk stratification based on genotype, ECG phenotype, clinical history, age, sex, concomitant diseases, drug therapies, and family history for syncope or sudden cardiac death. The therapeutic approaches for LQTS are multimodal. Prevention is the basis of the therapy and includes avoiding known risk factors / and potentially QT-prolonging drugs, and a pharmacological treatment with non-selective beta blockers. According to the risk profile and to the patient’s lifestyle the implantation of an ICD or a pacemaker should be considered.

What is known and objective Vitamin K deficiency is known to cause impaired coagulation. We report a case of marked prolongation of the prothrombin time-international normalized ratio (PT-INR) associated with warfarin and vitamin K deficiency caused by endoscopic nasobiliary drainage (ENBD). Case presentation Oral administration of warfarin was initiated in a 67-year-old man after left hemihepatectomy. He developed a biliary fistula after surgery that was treated by ENBD, which resulted in significant prolongation of the PT-INR. What is new and conclusion The effect of warfarin was enhanced in this patient due to reduced absorption of vitamin K as a result of external biliary drainage.

The QT interval represents the duration of ventricular depolarization and repolarization. It is measured from the beginning of the QRS complex to the end of the T wave. Prolongation of the QT interval may be congenital or acquired. This increases the risk of polymorphic ventricular tachycardia (i.e torsades de pointes) and cardiac arrest. To increase the awareness of this life-threatening phenomenon I outline an illustrative case in which acquired prolongation of the QT interval due to electrolyte derangement and administration of ciprofloxacin resulted in cardiac arrest due to torsade de pointes. Management of a patient with a long QT syndrome includes Immediate cessation of drugs that prolong the QT interval; cardiac monitoring, serial 12 lead ECGs and transthoracic echocardiography; measurement of serum electrolytes; intravenous potassium replacement; intravenous magnesium replacement; beta-blockade. Causes of acquired prolongation of the QT interval are common in critically ill patients. It is important to recognize this and consider screening with 12 lead ECG to reduce the risk of life-threatening ventricular arrhythmias.

Objective: In hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer (MBC), endocrine therapy (Tx) combined with an inhibitor of cycline-dependent kinases 4/6 (CDK4/6i) has now widely been accepted as the new standard-of-care in the first- and second-line setting. Among different agents available, the CDK4/6i ribociclib (RIBO) has been documented to be able to prolong cardiac repolarization as measured by the corrected QT interval (QTc). Cardiac monitoring by consecutive echocardiograms (ECGs) is thus recommended in MBC patients (pts) while being on RIBO treatment. However, little is known about the incidence and severity of QTc prolongation during RIBO therapy which should thus be further analyzed in the present investigation. Methods: A total of 29 pts were included, 7 pts were premenopausal and 22 were postmenopausal. All premenopausal pts underwent ovarian suppression with goserelin (ZOL). Endocrine treatment consisted of letrozole (LET) in 23 pts, exemestane (EXE) in 1 pt and fulvestrant (FULV) in 5 pts. In all pts, QTc was measured at start of RIBO and thereafter every 2-4 weeks (wks) for a maximum of 262 days while being on treatment. Mean QTc values were calculated at baseline (BL) and at 6 consecutive time points: #1 (d7-21 from BL), #2 (22-42d from BL), #3 (d43-63 from BL), #4 (d64-84 from BL), #5 (d85-105 from BL), #6 (d105-126 from BL). Changes of mean QTc values were analyzed with repeated measure ANOVA with p≤0.05 indicating statistical significance. Results: QTc showed a slight but not significant increase during RIBO Tx (p=0.306) with a maximum at #3. Whenever observed, QTc prolongation did not exceed 110% from BL in all but 4 pts. In the latter, QTc returned to normal values in all but 1 pt. OTc exceeding 480 ms were not observed at any time of the observation time. At BL, 17 pts had a normal ECG whereas 9 pts had preexisting ECG abnormalities other than long QT syndrome. 3 pts with normal ECG at BL developed ECG abnormalities during Tx with RIBO. No patient experienced a significant deterioration of cardiac ejection fraction while being on Tx. Conclusion: Clinically meaningful QTc prolongations did not occur in this real-world population of MBC pts treated with RIBO and endocrine agents. Moreover, cardiac function did not deteriorate during RIBO Tx neither in patients with normal ECG nor in those with (preexisting or newly diagnosed) ECG abnormalities. QTc prolongations induced by RIBO may thus be of minor importance in the clinical routine and the necessity of intensive ECG monitoring in pts subjected to RIBO is thus a matter of debate. Citation Format: Christian M Kurbacher, Alexander Schott, Ann T Kurbacher, Susanne Herz, Lotta A Fischer, Jutta A Kurbacher, Mathias Warm. QT-interval prolongation during the treatment with ribociclib and endocrine agents in patients with hormone receptor-positive, human epidermal growth factor 2-negative metastatic breast cancer: A real-world experience [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-22.

Diabetes mellitus (DM) is associated with increased risk of sudden cardiac death, but its role in arrhythmogenesis is not clear. We evaluated contributions of DM duration and hyperglycemia level to development of proarrhythmic electrophysiological changes in the experimental ischemia/reperfusion model. Ventricular epicardial 64-lead mapping and arrhythmia susceptibility burst-pacing testing were performed in 43 healthy and 55 diabetic (alloxan model) anesthetized rabbits undergoing 15 min left anterior descending coronary artery occlusion, followed by 15 min reperfusion. During ischemia, arrhythmia inducibility did not differ between the groups, but the number of reperfusion ventricular tachycardias and (or) fibrillations (VT/VFs) were higher in the DM group (14 out of 55) as compared with control (3 out of 43, p = 0.017). In the diabetic animals, both DM duration and glucose concentration were associated with reperfusion VT/VF development in univariate logistic regression analysis (odds ratio (OR) 1.058, 95% confidence interval (CI) 1.025–1.092, p < 0.001; and OR 1.119, 95% CI 1.045–1.198, p = 0.001, respectively). Only the DM duration, however, remained an independent predictor of reperfusion VT/VF in multivariate logistic regression analysis (OR 1.060, 95% CI 1.006–1.117, p = 0.029). Among mapping parameters, DM duration was associated with the prolongation of total ventricular activation duration (regression coefficient 0.152, 95% CI 0.049–0.255, p = 0.005) and activation-repolarization intervals (ARIs) (regression coefficient 0.900, 95% CI 0.315–1.484, p = 0.003). The prolonged ARI was the only mapping characteristic predicting reperfusion VT/VF development (OR 1.028, 95% CI 1.009–1.048, p = 0.004). The DM duration-dependent prolongation of ventricular repolarization presents a link between DM development and reperfusion VT/VF inducibility.

“Torsades de pointes”, a life-threatening rhythm disorder, is a polymorphic ventricular tachycardia that usually develops in association with a prolonged QT interval. Fluconazole, an anti-fungal drug, may also induce QT prolongation, in some cases subsequent torsades de pointes. Herein, we report a 16-year-old female presenting “torsades de pointes” after administration of fluconazole and rapidly improved upon cessation of the drug.

Background Oliceridine is a biased ligand at the μ-opioid receptor recently approved for the treatment of acute pain. In a thorough QT study, corrected QT (QTc) prolongation displayed peaks at 2.5 and 60 minutes after a supratherapeutic dose. The mean plasma concentration peaked at 5 minutes, declining rapidly thereafter. Objective The purpose of this study was to examine the basis for the delayed effect of oliceridine to prolong the QTc interval. Methods Repolarization parameters and tissue accumulation of oliceridine were evaluated in rabbit left ventricular wedge preparations over a period of 5 hours. The effects of oliceridine on ion channel currents were evaluated in human embryonic kidney and Chinese hamster ovary cells. Quinidine was used as a control. Results Oliceridine and quinidine produced a progressive prolongation of the QTc interval and action potential duration over a period of 5 hours, paralleling slow progressive tissue uptake of the drugs. Oliceridine caused modest prolongation of these parameters, whereas quinidine produced a prominent prolongation of action potential duration and QTc interval as well as development of early afterdepolarization (after 2 hours), resulting in a high torsades de pointes score. The 50% inhibitory concentration values for the oliceridine inhibition of the rapidly activating delayed rectifier current (human ether a-go-go current) and late sodium channel current were 2.2 and 3.45 μM when assessed after traditional acute exposure but much lower after 3 hours of drug exposure. Conclusion Our findings suggest that a gradual increase of intracellular access of drugs to the hERG channels as a result of their intracellular uptake and accumulation can significantly delay effects on repolarization, thus confounding the assessment of QT interval prolongation and arrhythmic risk when studied acutely. The multi-ion channel effects of oliceridine, late sodium channel current inhibition in particular, point to a low risk of devloping torsades de pointes.

Medication-induced prolongation of the QT-interval (miQTP) can lead to cardiac arrhythmia. Our aim was to investigate the prevalence of forensic autopsy cases where fatal cardiac arrhythmia related to treatment with QT-prolonging medications (QT-PMs) could be suspected. We performed a cross-sectional study of 741 forensic autopsies undertaken at our institution in non-drug addicts aged 15 years or above from 2017-2019. We defined a high risk of miQTP by one detected QT-PM in a concentration above therapeutic level, or two or more detected QT-PMs in post mortem blood. We reviewed the autopsy reports from cases with a high miQTP-risk to identify cases with no other apparent cause of death. We discarded suicides and cases with lethal levels of QT-PMs. We identified 167 cases (22.5%) with high risk of miQTP, and discarded 36 suicides (4.9%) and 7 (0.9%) with lethal levels of QT-PMs. Apart from a high risk of miQTP, no other apparent explanation of the cause of death was present in seven (0.9%). In 18 cases (2.4%) with high miQTP-risk, the cause of death was primarily attributed to cardiac changes other than acute cardiovascular events. In conclusion, 22.5% had a high risk of miQTP, and fatal cardiac arrhythmia related to treatment with QT-PMs could be suspected in 0.9%. However, a genetic pro-arrhythmic background could not be excluded in our study. Furthermore, it is possible that QT-PMs could have played a role in some of the 2.4% of cases where the cause of death was mainly attributed to cardiac changes and the risk of miQTP was high.

Diphenhydramine is a widely available, over-the-counter medication used for allergies and as a sleeping aid. When used in prescription doses, it is generally safe. Overdose of the medication has been associated with dangerous and life-threatening outcomes. Our case describes diphenhydramine toxicity manifesting with two rare but potentially life-threatening complications, rhabdomyolysis, and QT prolongation. Laboratory testing for diphenhydramine levels are not widely available. We recommend a high degree of suspicion for these complications when evaluating patients with diphenhydramine overdose, to adequately manage and prevent untoward outcomes.

Introduction Antiretrovirals have immensely increased the average life expectancy of HIV-positive patients. However, the incidence of QT interval prolongation and other arrhythmias has also increased. Methods Pubmed and Google Scholar were searched for relevant literature published between 1990 and 2019. Results and discussion HIV-positive patients with high viral load, low CD4 count, chronic inflammation, and autonomic neuropathy can develop QT interval prolongation. Another factor prolonging QT interval includes exposure to the HIV transactivator protein, which inhibits hERG K (+) channels controlling IKr K (+) currents in cardiomyocytes. Protease inhibitors inhibiting the CYP3A4 enzyme can also lead to QT interval prolongation. QT interval prolongation can potentially be exacerbated by opioids, antipsychotics, antibiotics, and antifungals, the adjunct medications often used in HIV-positive patients. Hepatic insufficiency in seropositive patients on antiretrovirals may also increase the risk of QT interval prolongation. Conclusion Baseline and follow-up EKG in the susceptible population is suggested.

Introduction: The frequency of QT interval prolongation as published in the international and local literature has been variable. Aims & Objectives: To determine the frequency of QT interval prolongation in patients with chronic liver disease and resolve the variability in the literature. Place and duration of study: The present study was conducted in Gastroenterology and Hepatology Unit Shaikh Zayed Hospital Lahore from 1st March 2017 to 31st August 2017. Material & Methods: About 240 patients with diagnosed chronic liver disease were selected. Electrocardiography (12 lead) was performed in all patients to look for QT interval prolongation and their mean was calculated for purpose of analysis. Results: Mean age of our patients was 53.7±11.9 and male gender was dominant (55.8%). It was noted that QT interval was prolonged in 62 patients (25.8%) while rest of the 178 patients had normal QT interval. Conclusion: QT interval prolongation is frequently observed (25.8%) in chronic liver disease patients. Therefore, every patient with chronic liver disease should be investigated for QT interval prolongation. Key words: Chronic liver disease, QT interval, Electrocardiography

Background Determination of the prolonged QT interval in left bundle branch block (LBBB), which should be of special concern to identify individuals at high risk of potentially fatal cardiac arrhythmia risk, has been problematic. Methods Electrocardiograms (ECGs) (n = 17) in intermittent LBBB were used to develop a new formula for the calculation of QTc in LBBB. This formula and 5 others were compared in a population with LBBB (n = 2610). The QT was corrected for heart rate (HR) using the Bazett formula (QTcBZT) and the spline QT formula (QTcRBK), which is relatively independent of HR. The JT interval was significantly related to HR. Results The new approach (QTcLBBBNEW = 0.945*QTcRBKLBBB − 26) in LBBB showed the highest correlation with intrinsic QTc (without LBBB) and had minimal HR dependency. Previous formulae to determine the QT interval in LBBB showed significant HR dependency except for one proposed by Rautaharju et al. Inclusion of an HR correction factor in existing formulae blunted HR dependency but not if the QT interval was adjusted by the QTcBZT. In men and women, use of the QTcBZT markedly increases the proportion of individuals with prolonged QTc, which was more evident with increasing HR. The 99th and 97.5th percentiles for QTcLBBBNEW for men and women identified abnormal QT prolongation in LBBB. Conclusions A new formula that modifies the QT and JT intervals in LBBB predicts the QT interval in the absence of LBBB. Abnormal QT intervals in the 99th and 97.5th percentiles can identify patients with LBBB who have QT interval prolongation.

Prolonged QT intervals are a major risk factor for ventricular arrhythmias and a leading cause of sudden cardiac death. Various drugs are known to trigger QT interval prolongation and increase the proarrhythmic potential. Yet, how precisely the action of drugs on the cellular level translates into QT interval prolongation on the whole organ level remains insufficiently understood. Here we use machine learning techniques to systematically characterize the effect of 30 common drugs on the QT interval. We combine information from high fidelity three-dimensional human heart simulations with low fidelity one-dimensional cable simulations to build a surrogate model for the QT interval using multi-fidelity Gaussian process regression. Once trained and cross-validated, we apply our surrogate model to perform sensitivity analysis and uncertainty quantification. Our sensitivity analysis suggests that compounds that block the rapid delayed rectifier potassium current I Kr have the greatest prolonging effect of the QT interval, and that blocking the L-type calcium current I CaL and late sodium current I NaL shortens the QT interval. Our uncertainty quantification allows us to propagate the experimental variability from individual block-concentration measurements into the QT interval and reveals that QT interval uncertainty is mainly driven by the variability in I Kr block. In a final validation study, we demonstrate an excellent agreement between our predicted QT interval changes and the changes observed in a randomized clinical trial for the drugs dofetilide, quinidine, ranolazine, and verapamil. We anticipate that both the machine learning methods and the results of this study will have great potential in the efficient development of safer drugs.

dl-Sotalol which can block both K+ channel and s-adrenoceptor has been shown to prolong the J–Tpeakc of electrocardiogram in beagle dogs but tended to shorten it in microminipigs, although the drug prolonged the QT interval in both animals under physiologically maintained experimental condition. In order to estimate how the changes in the J–Tpeakc in the normal hearts would be reflected in the pathologic hearts, we compared proarrhythmic effects of dl-sotalol by using proarrhythmia models of beagle dogs and microminipigs, of which atrioventricular node had been ablated > 2 months and 8–9 weeks before, respectively (n = 4 for each species). dl-Sotalol in an oral dose of 10 mg/kg induced torsade de pointes in three out of four beagle dogs, which degenerated into ventricular fibrillation. In microminipigs, the same dose did not trigger torsade de pointes at all, whereas intermittent ventricular pauses were observed in each animal after the drug treatment. These results indicate that assessment of the J–Tpeakc along with the QT-interval prolongation in healthy subjects may provide reliable information of risk prediction for patients susceptible to the drug-induced torsade de pointes.

Background: The Cockcroft-Gault formula is recommended to determine a renal indication for dose reduction of dabigatran, edoxaban, and rivaroxaban. Nephrology guidelines now recommend the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae as more accurate estimates of glomerular filtration rate. Methods: We analyzed anticoagulated patients with atrial fibrillation who were enrolled in the Prevention of Thromboembolic Events – European Registry in Atrial Fibrillation (PREFER in AF). The proportion of patients with dissimilar renal dosing indications was assessed when applying Cockcroft-Gault, MDRD, or CKD-EPI. Thromboembolic and major bleeding events at 1 year were compared in patients in whom Cockcroft-Gault and CKD-EPI provided concordant or discordant results around a threshold of 50 mL/minute. Results: Out of 1288 patients with atrial fibrillation with chronic kidney disease in whom Cockcroft-Gault suggested a dose reduction of dabigatran, edoxaban, or rivaroxaban (creatinine clearance ≤50 mL/minutes), 19% and 16% were reclassified to the respective higher doses, and 24% and 23% to the respective lower doses by applying the MDRD and CKD-EPI formulae, respectively. In patients potentially receiving a different dose of dabigatran, edoxaban, or rivaroxaban when using CKD-EPI, we observed an excess of thromboembolic events (4.1% versus 0.8%; odds ratio, 5.5 [95% CI, 1.5–20.8]; P =0.01). Major bleeding rates were nonsignificantly different in the discordance versus concordance group (5.7% versus 2.7%; odds ratio, 2.2 [95% CI, 0.9–5.6]; P =0.09). Conclusions: The MDRD and CKD-EPI formulae suggest a different dosing in up to a quarter of anticoagulated patients with atrial fibrillation. This seems to impact hard outcomes.

Background Electrocardiographic abnormalities, such as PR interval prolongation, have been anecdotally reported in patients with aortic root abscess (ARA). An electrocardiographic marker may be useful in identifying those patients with aortic valve endocarditis who may progress to ARA. The objective of this study is to evaluate the change in the PR interval in patients with surgically confirmed ARA and compare it to age‐ and gender‐matched controls with echocardiographically or surgically confirmed aortic valve endocarditis but without aortic root abscess and those hospitalized with diagnoses other than endocarditis. Methods Patients were eligible for enrollment if they were 18 years or older and were hospitalized for either ARA, aortic valve endocarditis, or for unrelated reasons and had at least one 12‐lead electrocardiogram (ECG) prior to or on the day of hospitalization and at least one ECG after hospitalization but prior to any cardiac surgical procedure. Delta PR interval, defined as the difference between the pre‐ and post‐admission PR interval, was the primary outcome of interest. The patients in the ARA group were age‐ and gender‐matched to patients with aortic valve endocarditis and to those without endocarditis. Comparisons of demographic variables and study outcomes were performed. Results Eighteen patients with surgically confirmed ARA were enrolled. These patients were age‐ and gender‐matched to 19 patients with aortic valve endocarditis and 18 patients with no past history or evidence of endocarditis during hospitalization. No difference was noted in the baseline PR interval between the groups. However, the PR interval following admission in the aortic root abscess group (201 ± 66 ms) was significantly longer than the PR interval in both the aortic valve endocarditis (162 ± 27 ms) (24%, p = .009) and no endocarditis (143 ± 24 ms) (40%, p

Torsade de points (TdP), a life-threatening arrhythmia that can increase the risk of sudden cardiac death, is associated with drug-induced QT-interval prolongation on the electrocardiogram (ECG). While many modern ECG machines provide automated measurements of the QT-interval, these automated QT values are usually correct only for a noise-free normal sinus rhythm, in which the T-wave morphology is well defined. As QT-prolonging drugs often affect the morphology of the T-wave, automated QT measurements taken under these circumstances are easily invalidated. An additional challenge is that the QT-value at risk of TdP varies with heart rate, with the slower the heart rate, the greater the risk of TdP. This paper presents an explainable algorithm that uses an understanding of human visual perception and expert ECG interpretation to automate the detection of QT-prolongation at risk of TdP regardless of heart rate and T-wave morphology. It was tested on a large number of ECGs (n = 5050) with variable QT-intervals at varying heart rates, acquired from a clinical trial that assessed the effect of four known QT-prolonging drugs versus placebo on healthy subjects. The algorithm yielded a balanced accuracy of 0.97, sensitivity of 0.94, specificity of 0.99, F1-score of 0.88, ROC (AUC) of 0.98, precision-recall (AUC) of 0.88, and Matthews correlation coefficient (MCC) of 0.88. The results indicate that a prolonged ventricular repolarisation area can be a significant risk predictor of TdP, and detection of this is potentially easier and more reliable to automate than measuring the QT-interval distance directly. The proposed algorithm can be visualised using pseudo-colour on the ECG trace, thus intuitively ‘explaining’ how its decision was made, which results of a focus group show may help people to self-monitor QT-prolongation, as well as ensuring clinicians can validate its results.

We herein report the case of a 20-year-old man with a history of epilepsy who presented with frequent transient loss of consciousness (T-LOC) and polymorphic ventricular tachycardia (VT) with QT interval prolongation. Blood investigations revealed panhypopituitarism. Following a biopsy, he was diagnosed with brain germinoma. During the biopsy, he had an episode of polymorphous VT with QT prolongation. There was no recurrence of T-LOC following chemotherapy and hormone replacement therapy. This case indicates the importance of checking the QT interval in patients with T-LOC, including those with seizures and brain tumors, to ensure appropriate treatment.

Multidrug resistant tuberculosis (MDR-TB) and non-tuberculous mycobacterium (NTM) infections present challenges due to complex treatment regimens Extended use of multiple antibiotics exposes patients to higher risks of side effects from anti-mycobacterial medications A high drug toxicity profile necessitates closer monitoring One of the more challenging issues is QTc prolongation with non-injectable regimens This study investigates the portable AliveCor device and Kardia app to record and measure the QT interval on a 6-lead ECG This handheld device can record an ECG trace in a minimum of 30 seconds by establishing three points of contact with electrodes to skin: two thumbs and left ankle or knee A 6-Lead ECG by AliveCor was recorded for each patient at risk of QT prolongation (n=16) and compared to the existing 12-Lead ECG The automated QTc readout from the 12-Lead ECG for each patient and mean QTc value calculated from each patients' respective AliveCor tracing were shown alongside each other (figure 1) The general trend suggests the AliveCor underestimates the QTc as 12/13 cases (92%) calculated the AliveCor QTc as lower than their corresponding 12-Lead QTc readout The mean%difference between the automated 12-Lead and manually calculated AliveCor readings was 3% The largest%difference between the two readings was 12% The larger discrepancies could be reflected by the varying quality of the AliveCor tracings Three patients were excluded due to poor tracings or lack of corresponding 12-Lead ECG This study aimed to provide pilot data and evaluate the feasibility of a portable device to monitor QTc intervals for patients on potential cardiotoxic medications It has allowed us to place in context the role for mobile monitoring in (Figure presented) modern-day clinical practice Moreover, the recent COVID-19 pandemic has seen increasing relevance for remote monitoring Remote monitoring can aid progression of treatment whilst protecting vulnerable patients from risk of exposure to illness The use of AliveCor could potentially be translated into current clinical practice using calculated QTcs from the device with caution of percentage variation either side This could facilitate the use of AliveCor as a promising and convenient screening tool before further evaluation by a 12-Lead ECG is required

Introduction Polymorphic ventricular tachycardia (VT) is defined as a rapid rhythm with continuously changing ventricular activation. In the absence of QT interval prolongation, its evaluation is a challenging activity with a series of differential diagnoses. The present study reports on a case of a young man who had an out-of-hospital cardiac arrest and and who later presented an episode of exercise-induced polymorphic VT. A rational investigation is discussed based on the patient’s clinical findings and baseline ECG. […] Cardiac Arrest [...]

Background Insulin-induced hypoglycemia has been demonstrated to prolong the corrected QT (QTc) interval. Prolongation of the QTc interval, especially in diabetic patients using insulin, can cause fatal ventricular arrhythmias. The aim of this study was to evaluate the effects of metoprolol, diltiazem, and pilocarpine on hypoglycemia-induced QTc prolongation. Methods Thirty male rats were randomly distributed into the following five groups: Group 1 (1 mL/kg saline, n=6), Group 2 (40 U/kg crystalline insulin + saline, n=6), Group 3 (40 U/kg crystalline insulin + 1 mg/kg metoprolol, n=6), Group 4 (40 U/kg crystalline insulin + 0.8 mg/kg pilocarpine, n=6), and Group 5 (40 U/kg crystalline insulin + 2 mg/kg diltiazem, n=6). Three hours after insulin injection, the blood glucose level was measured in all groups. Blood glucose

Clot waveform analysis based on activated partial thromboplastin time (aPTT) is reported to be a useful assay. We attempted to find beneficial parameters with the first-derivative curve. We examined 106 plasma samples with prolonged aPTT and analyzed the first-derivative curve statistically by dividing it into 6 groups (Lupus anticoagulant, Heparin, Direct oral anticoagulants, Factor VIII inhibitor, Hepatic dysfunctions and Factor deficiency). We obtained 7 coordinates for parameter measurement by analyzing the first-derivative curve and set 20 parameters including the velocity axis, the time axis, and area parameters. The distribution was checked by extracting each parameter that showed the most significant difference in the 6 groups. As a result, it was revealed that we could classify aPTT prolongation by using a combination of 3 parameters, the initial-to-peak gradient, the ratio initial-to-intermediate velocity/intermediate-to-peak velocity, and the initial-to-peak area size. We constructed a flowchart combining these 3 parameters and were able to discriminate 75% of the specimens. These parameters derived from the first-derivative curve of clot waveform analysis are useful tools to discriminate aPTT prolongation.

[EN] The prolongation of the QT interval represents the main feature of the long QT syndrome (LQTS), a life-threatening genetic disease. The heterozygous SCN5A V411M mutation of the human sodium channel leads to a LQTS type 3 with severe proarrhythmic effects due to an increase in the late component of the sodium current (INaL). The two sodium blockers flecainide and ranolazine are equally recommended by the current 2015 ESC guidelines to treat patients with LQTS type 3 and persistently prolonged QT intervals. However, awareness of pro-arrhythmic effects of flecainide in LQTS type 3 patients arose upon the study of the SCN5A E1784K mutation. Regarding SCN5A V411M individuals, flecainide showed good results albeit in a reduced number of patients and no evidence supporting the use of ranolazine has ever been released. Therefore, we ought to compare the effect of ranolazine and flecainide in a SCN5A V411M model using an in-silico modeling and simulation approach. We collected clinical data of four patients. Then, we fitted four Markovian models of the human sodium current (INa) to experimental and clinical data. Two of them correspond to the wild type and the heterozygous SCN5A V411M scenarios, and the other two mimic the effects of flecainide and ranolazine on INa. Next, we inserted them into three isolated cell action potential (AP) models for endocardial, midmyocardial and epicardial cells and in a one-dimensional tissue model. The SCN5A V411M mutation produced a 15.9% APD90 prolongation in the isolated endocardial cell model, which corresponded to a 14.3% of the QT interval prolongation in a one-dimensional strand model, in keeping with clinical observations. Although with different underlying mechanisms, flecainide and ranolazine partially countered this prolongation at the isolated endocardial model by reducing the APD90 by 8.7 and 4.3%, and the QT interval by 7.2 and 3.2%, respectively. While flecainide specifically targeted the mutation-induced increase in peak INaL, ranolazine reduced it during the entire AP. Our simulations also suggest that ranolazine could prevent early afterdepolarizations triggered by the SCN5A V411M mutation during bradycardia, as flecainide. We conclude that ranolazine could be used to treat SCN5A V411M patients, specifically when flecainide is contraindicated., This work was partially supported by Fondo Europeo de Desarrollo Regional (FEDER, "Union Europea, Una forma de hacer Europa") with the Ministerio de Economia y Competitividad (DPI2015-69125-R), Direccion General de Politica Cientifica de la Generalitat Valenciana (PROMETEO/2020/043) and Instituto de Salud Carlos III (La Fe Biobank PT17/0015/0043), as well as by Vicerrectorado de Investigacion, Innovacion y Transferencia de la Universitat Politecnica de Valencia with Ayuda a Primeros Proyectos de Investigacion (PAID-06-18), and by Memorial Nacho Barbera.

Background and aims High rates of sudden cardiac death are mostly attributed to ventricular arrhythmias including QTc prolongation in hemodialysis patients. We aimed to investigate the correlation of electrolyte and volume changes with QTc interval prolongation in hemodialysis patients. Study design The present study is designed as a cross-sectional study. Methods The study was conducted at the hemodialysis unit of a training and research hospital and its' satellite dialysis unit. Patients were divided into three groups. Group-1: with normal QTc interval both at the beginning and during dialysis session; group-2: with prolonged QTc interval at the beginning and remained prolonged during dialysis session; group-3: with normal QTc interval at the beginning but prolonged during the dialysis session. In addition, patients were evaluated in terms of QTc change between the beginning and 2nd hour (delta-QTc-1) and between 2nd hour and 4th hour (delta-QTc-2), respectively, and defined as 'patients with increased QTc interval' and 'patients without increased QTc interval'. Results A total of 45 prevalent hemodialysis patients were enrolled in the study. 14 patients (31.1%) had normal QTc interval (group-1), 13 patients (28.9%) had prolonged QTc interval at the beginning and remained prolonged during dialysis session (group-2) and 18 patients (40%) had normal QTc interval at the beginning but prolonged during dialysis session (group-3). There was no statistically significant difference between groups in terms of baseline electrolyte levels. Calcium change in the first 2 h was lower in patients with QTc prolongation from the start or during the dialysis session (group-2 and group-3). In addition, systolic blood pressure (SBP) levels at the beginning of the session (118 ± 15 mmHg vs 124 ± 28 mmHg vs138 ± 24 mmHg; p = 0.04) and intradialytic ultrafiltration (UF) rate were higher (1.96 ± 0.6 L/4 h vs 2.6 ± 1.0 L/4 h vs 2.8 ± 0.9 L/4 h; p = 0.03) in group-2 and group-3 compared to patients in group-1. Increase in QTc interval was found higher in patients with less calcium increase (Rho: - 0.36; p = 0.01) and with greater magnesium decrease in the first 2 h (Rho: 0.31; p = 0.04). Conclusion QTc interval prolongation is common among hemodialysis patients. High intradialytic UF rates, change in serum magnesium and calcium levels in the first 2 h were found associated with QTc prolongation. However, QTc prolongation was found independently associated only with UF volume and calcium change in the first 2 h.

Background: Cardiovascular complications are common in chronic kidney disease (CKD) patients. Endothelial nitric oxide synthase (eNOS) is very important for the homeostasis of the cardiovascular system, and its gene polymorphism at position 894 (G>T) has not been investigated with QTc interval in patients on dialysis. Objective: This study evaluated the association of the 894G>T polymorphism with QTc prolongation and endothelial dysfunction risk in dialysis patients. Methods: Predialysis blood samples were collected for eNOS gene polymorphism, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), total antioxidant, asymmetric dimethylarginine (ADMA) and L-arginine, and 12-lead electrocardiograms were analyzed in these patients. Statistics were based on continuous and categorical variables using Fisher’s exact or Chi-square or one-way ANOVA or KruskalWallis tests. The results were considered significant when P < 0.05. Results: The study showed that the GG genotype was prevalent, with 54% of patients, followed by 41% GT and 6% TT, and the genotypic distribution was not associated with QTc prolongation. Furthermore, patients with the T allele showed increased ADMA, L-arginine and peroxidation lipid levels with reduced NO synthesis. Conclusion: Our study showed a lack of association between QTc interval and eNOS polymorphism; however, it was found that patients with the T allele had a greater risk of developing endothelial dysfunction by ADMA, which could contribute to future cardiovascular complications and worsening of CKD.

The aim of this study is to analyze whether soluble fms-like tyrosine kinase-1 (sFlt-1) can be correlated with the severity of PE.This study was conducted in a single hospital and is a prospective, observational study. sFlt-1 was measured at the diagnosis of preeclampsia. The period from diagnosis to pregnancy termination (pregnancy prolongation periods) was defined as the barometer for the severity of PE. The correlations between sFlt-1 level with pregnancy prolongation periods were then analyzed.Eighteen pregnant women diagnosed with early-onset preeclampsia were recruited. sFlit-1 value significantly negatively correlated with the pregnancy prolongation period from diagnosis (sFlt-1 was correlated with the pregnancy prolongation periods after onset of PE. sFlt-1 in early-onset PE may reflect the severity of PE in pregnant women.

Conventional MRI studies have reported several structural changes such as brain atrophy and ventricular enlargement in healthy aging. Quantitative MRI (qMRI) allows the measurement of tissue characteristics such as the longitudinal relaxation times (T 1 ) which provides unique and complementary information to widely used measures of brain signal characteristics. In this study, the T 1 values on entire brain were mapped with an ROI based method. T 1 prolongation with aging was demonstrated on numerous cortical and subcortical areas such as caudate, thalamus and prefrontal cortex. This outcome was interpreted as increased demyelination in these structures.

Introduction: First-degree atrioventricular block (fAVB) is a common cardiac conduction disorder diagnosed by prolongation of the PR interval ≥220 msec. Although it is generally considered benign, some previous studies demonstrated that fAVB was associated with incident atrial fibrillation (AF). However, evidence is scarce regarding the association between fAVB and incident AF in older populations. Hypothesis: We hypothesized that fAVB was significantly associated with incident AF in older populations. Methods: Eligible participants were residents in Kanazawa City who aged ≥ 40 years and underwent 12-lead ECG at the national Japanese health checkups in 2013. Participants with AF detected at the baseline exam and with no follow-up examinations between 2014 and 2018. fAVB was defined as PR interval ≥ 220 msec based on the Minnesota code (6-3). Incident AF was defined as the first episode of AF detected by 12-lead ECG at the annual health checkups. The cumulative incidence of AF was estimated by the Kaplan Meier curve analysis, and statistical significance was evaluated by the log-rank test. Unadjusted and adjusted hazard ratios (HRs) were computed by the Cox proportional hazard model. HRs were adjusted using three models in which conventional risk factors for AF were included (Table). Results: 37,730 participants (mean age, 72.3 ± 9.6 years; Male, 37%) were included. Baseline fAVB was observed in 667 (1.8%) participants. During the median follow-up period of 5 years (interquartile range, 4.0 - 5.0 years), 691 cases of incident AF were observed. Kaplan Meier curve showed that a 5-year cumulative incidence of AF was significantly higher in fAVB (+) group compared with fAVB (-) group (6.8% vs 2.1%, p < 0.01). In the fully adjusted model, fAVB was significantly associated with incident AF (HR, 1.75; 95% confidence interval, 1.25 - 2.45; p-value < 0.01) (Table). Conclusion: fAVB was independently associated with incident AF in this predominantly elderly Japanese population.

The prevalence of arrhythmias varies in COVID-19. In a study of 138 patients from Wuhan, who were hospitalized with COVID-19 related pneumonia, arrhythmias were reported in 17% of the general cohort and in 44% of patients admitted to an intensive care unit

Background PR prolongation is associated with poor hemodynamic performance and may contribute to heart failure (HF). There is some evidence that in HF patients, normalization of atrioventricular (AV) coupling can attenuate HF. Purpose To investigate acute hemodynamic effects of restoration of AV coupling by atrio-biventricular (BiV) pacing in patients with HF and PR prolongation, but without evident ventricular dyssynchrony. Methods Nineteen patients underwent BiV pacemaker implantation. An invasive hemodynamic pacing protocol was performed during BiV and right ventricular (RV) pacing with four paced AV delays (100, 75, 50 and 25% of patient's PR interval during baseline AAI pacing). All patients had symptomatic HF, left ventricular ejection fraction (LVEF) 150 ms or left bundle branch block. Acute hemodynamic response was assessed by invasive left ventricular (LV) stroke work measurements (conductance catheter technique). Results At baseline, PR interval was 255±22 ms, QRS duration 122±19 ms and LVEF 29±6%. Reducing AV delay to 50% of patient's intrinsic PR interval by BiV pacing resulted in a median 25% increase (p Conclusion In patients with HF and PR prolongation, BiV pacing can be used to improve AV coupling that leads to hemodynamic improvement. These results suggest that BiV pacing may also be beneficial in this subset of HF patients that are currently not indicated for CRT. ReachPR Trial Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Abbott funded a part of this study.