Search Results (189)

New approach methodologies (NAMs), including microphysiological systems (MPSs), can recapitulate structural and functional complexities of organs. Vanoxerine was reported to induce cardiac adverse events, including torsade de points (TdP), in a Phase III clinical trial. Despite earlier nonclinical animal models and Phase I–II clinical trials, events of QT prolongation or proarrhythmia were not observed. Here, we utilized cardiac NAMs to evaluate the functional consequences of vanoxerine treatment on human cardiac excitation–contraction coupling. The cardiac MPS used in this study was a microfabricated fluidic culture platform with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) capable of evaluating voltage, intracellular calcium handling, and contractility. Likewise, the hiPSC-CM comprehensive in vitro proarrhythmia assay (CiPA) was employed based on multielectrode array (MEA). Vanoxerine treatment delayed repolarization in a concentration-dependent manner and induced proarrhythmic events in both NAM platforms. The complex cardiac MPS displayed a frequency-dependent vanoxerine response such that EADs were eliminated at a faster pacing rate (1.5 Hz). Moreover, exposure analysis revealed a 99% vanoxerine loss in the cardiac MPS. TdP risk analysis demonstrated high to intermediate TdP risk at clinically relevant concentrations of vanoxerine and frequency-independent EAD events in the hiPSC-CM CiPA model. These findings demonstrate that nonclinical cardiac NAMs can recapitulate clinical outcomes, including detection of vanoxerine-induced delayed repolarization and proarrhythmic effects. Moreover, this work provides a foundation to evaluate the safety and efficacy of novel compounds to reduce the dependence on animal studies. Full article

Background: Pulmonary embolism (PE) increases right ventricular (RV) afterload, potentially leading to myocardial stress and electrocardiographic abnormalities. Although QTc prolongation has been suggested as a marker of RV dysfunction, its prevalence, clinical significance, and prognostic value in acute PE remain poorly defined. Objective: The objective of this study is to evaluate the prevalence and clinical implications of QTc prolongation in patients with intermediate–high and high-risk acute PE. Methods: We retrospectively analyzed 95 consecutive patients admitted with intermediate–high or high-risk PE between September 2021 and December 2023. QTc prolongation was defined as ≥470 ms in males and ≥480 ms in females. Clinical, imaging, and laboratory data were compared between patients with normal and prolonged QTc intervals. QTc was assessed at admission, after treatment, and prior to discharge. Results: QTc prolongation was observed in 28.4% of patients at presentation. This group had significantly higher lactate levels (2.3 vs. 1.8 mmol/L, p = 0.03) and a non-significant trend toward elevated troponin and lower oxygen saturation. No differences were observed in echocardiographic or CT-based RV dysfunction parameters. QTc values normalized by discharge irrespective of treatment modality. There was no association between QTc prolongation and in-hospital or long-term mortality. A trend toward more aspiration thrombectomy was noted in the prolonged QTc group (29.6% vs. 11.8%, p = 0.06). Conclusions: QTc prolongation is common in acute intermediate–high and high-risk PE and may reflect transient myocardial stress. While not predictive of clinical outcomes, it should be considered in the differential diagnosis of QTc prolongation in patients presenting with dyspnea and chest pain. Full article

Background/Objectives: ST-segment deviation (STD) on electrocardiography (ECG) may reflect myocardial injury in critically ill patients. However, its prognostic significance in non-cardiac intensive care unit (ICU) populations remains unclear. We aimed to assess the association between STD on ICU admission and 30-day mortality and to evaluate its incremental prognostic value beyond the SOFA score. Methods: In this retrospective single-center study, we included 307 consecutive ICU patients (median age: 64.0 years; 65.5% men). Patients with acute cardiac conditions were excluded. STD was defined as ≥1 mm ST elevation or depression in any lead on standard 12-lead ECG performed on admission. The primary outcome was 30-day all-cause mortality. Prognostic associations were assessed using multivariable Cox regression adjusted for SOFA score. Discriminative performance was evaluated by comparing ROC curves for models with and without STD, with bootstrap-based testing (1000 iterations) to assess significance. Results: STD was present in 126 patients (41.0%) and occurred more frequently in non-survivors (47.6% vs. 36.5%, p = 0.033. In Cox regression, STD was independently associated with 30-day mortality (HR = 1.534; 95% CI: 1.081–2.177; p = 0.017), even after adjustment for SOFA score. This association remained statistically robust in bootstrap validation. The addition of STD amplitude to the SOFA score modestly improved model discrimination with a borderline significant difference between the areas under the curve (ΔAUC = 0.005, p = 0.0581). Conclusions: ST-segment deviation on the admission ECG is an independent predictor of 30-day mortality in non-cardiac critically ill patients and may enhance risk stratification beyond the SOFA score. Full article

Objectives: With the growing importance of mobile technology and artificial intelligence (AI) in healthcare, the development of automated cardiac diagnostic systems has gained strategic significance. This review aims to summarize the current state of knowledge on the use of AI in the analysis of electrocardiographic (ECG) signals obtained from wearable devices, particularly smartwatches, and to outline perspectives for future clinical applications. Methods: A narrative literature review was conducted using PubMed, Web of Science, and Scopus databases. The search focused on combinations of keywords related to AI, ECG, and wearable technologies. After screening and applying inclusion criteria, 152 publications were selected for final analysis. Conclusions: Modern AI algorithms—especially deep neural networks—show promise in detecting arrhythmias, heart failure, prolonged QT syndrome, and other cardiovascular conditions. Smartwatches without ECG sensors, using photoplethysmography (PPG) and machine learning, show potential as supportive tools for preliminary atrial fibrillation (AF) screening at the population level, although further validation in diverse real-world settings is needed. This article explores innovation trends such as genetic data integration, digital twins, federated learning, and local signal processing. Regulatory, technical, and ethical challenges are also discussed, along with the issue of limited clinical evidence. Artificial intelligence enables a significant enhancement of personalized, mobile, and preventive cardiology. Its integration into smartwatch ECG analysis opens a path toward early detection of cardiac disorders and the implementation of population-scale screening approaches. Full article

Bedaquiline is known to shorten the duration of therapy of tuberculosis but has limitations, e.g., poor solubility and adverse effects such as prolongation of the QT interval. In this study, bedaquiline was incorporated into an inherently targeted nanosystem for improved permeation of the drug, with ex vivo diffusion studies performed to investigate its penetration. The bedaquiline-loaded mannan–chitosan oligosaccharide lactate nanoparticles were prepared by a one-step ionic gelation probe sonication method. A PermeGear 7-in-line flow-through diffusion system was used for the ex vivo diffusion studies across porcine and human pericardia. Bedaquiline-loaded nanoparticles with a particle size and potential of 192.4 nm and 40.5 mV, respectively, were obtained. The drug-loaded mannan–chitosan nanoparticles had an encapsulation efficacy of 98.7% and drug loading of 0.6%. Diffusion data indicated a steady-state flux of 2.889 and 2.346 µg.cm⁻².min⁻¹ for porcine and human pericardia, respectively. The apparent permeability coefficients were calculated to be 2.66 × 10⁻⁴ cm.min⁻¹ and 2.16 × 10⁻⁴ cm.min⁻¹ for porcine and human pericardia, respectively. The lag phases were 52.72 min and 0 min for porcine and human pericardia, respectively. The drug permeation indicated a consistent and linear diffusion pattern across both porcine and human pericardia, additionally approving the porcine pericardium as a great comparable tissue to human tissue for pericardial studies. This study is the first to demonstrate ex vivo diffusion of bedaquiline-loaded, macrophage-targeted chitosan–mannan nanoparticles across both human and porcine pericardia, representing a novel platform for disease-targeted, localized treatment of TB pericarditis. Full article

Background/Objectives: Long QT Syndrome type 2 (LQT2) is a cardiac channelopathy linked to pathogenic variants in the KCNH2 gene, which encodes the Kv11.1 potassium channel, essential for cardiac repolarization. Variants affecting splice sites disrupt potassium ion flow, prolong QT interval, and increase the risk of arrhythmias and sudden cardiac death (SCD). Understanding genotype–phenotype correlations is key, given the variability of clinical manifestations even within families sharing the same variant. We aimed to evaluate new pathogenic variants by analyzing genotype–phenotype correlations in informative families. Methods: Genetic and clinical assessments were performed on index cases and family members carrying KCNH2 pathogenic variants, referred for genetic testing between 2010 and June 2023. The next-generation sequencing (NGS) of 210 cardiovascular-related genes was conducted. Clinical data, including demographic details, family history, arrhythmic events, electrocardiographic parameters, and treatments, were collected. Results: Among 390 patients (152 probands) tested for LQTS, only 2 KCNH2 variants had over 5 carriers. The detailed clinical information of 22 carriers of this KCNH2 p.Ser261fs. has already been reported by our research group. Moreover, we identified 12 carriers of the KCNH2 c.77-2del variant, predicted to disrupt a splice site and not previously reported. Segregation analysis showed its high penetrance, supporting its classification as pathogenic. Conclusions: The newly identified KCNH2 c.77-2del variant is a pathogenic, as strongly supported by the segregation analysis. Our findings underscore the importance of further research into splice site variants to enhance clinical management and genetic counseling for affected families. Full article

Background/Objectives: Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in pediatric epilepsy. Cardiac arrhythmias, possibly reflected by electrocardiographic (ECG) abnormalities, are thought to contribute significantly to SUDEP risk. This study aimed to evaluate ECG indices associated with an increased risk of both atrial and ventricular arrhythmias and sudden cardiac death in pediatric patients with generalized and focal seizures, excluding those with underlying channelopathies. Materials and Methods: Pediatric patients aged 0–18 years with generalized or focal epilepsy followed at our center between October 2024 and April 2025 were enrolled. Comprehensive cardiac evaluations, including echocardiography and 12-lead ECG, were conducted. Patients with channelopathies, structural heart defects, or significant congenital heart disease were excluded. ECG parameters—QT dispersion (QT Disp), corrected QT interval (QTc), QTc dispersion (QTc Disp), P-wave dispersion (P Disp), and T peak-T end interval (Tp-e)—were analyzed across epilepsy subgroups and compared to healthy controls. Effects of antiepileptic drug (AED) use and gender were also assessed. Results: A total of 151 participants were included (generalized: n = 51; focal: n = 50; controls: n = 50). QTc and Tp-e intervals were prolonged in both epilepsy groups compared to controls (p = 0.001 and p = 0.036, respectively), however, they fell within the conventional parameters. AED use was associated with further prolongation of QTc (p = 0.035) and Tp-e (p = 0.037), these metrics were similarly found to be within the established normative boundaries. Phenobarbital and lamotrigine users showed the longest QTc, albeit not statistically significant. Males with generalized seizures had longer maximum P-wave duration (P Max) than females (p = 0.009). A moderate correlation was found between Tp-e and QTc (r = 0.557, p = 0.001). Conclusions: Although there are findings in our study that may suggest a relationship between SUDEP and arrhythmia according to electrocardiographic markers associated with arrhythmia risk, larger and prospective studies with long-term follow-up are needed in the future. Full article

The macrolide class of antibiotics are widely utilized in clinical settings for a broad range of bacterial infections and have additional roles as immunomodulatory agents. Although efficacious with a good safety profile overall, they have been associated with prolongation of the QT interval and development of the polymorphic ventricular tachycardia, Torsades de pointes (TdP). In a 2020 scientific statement, the American Heart Association (AHA) classified azithromycin, clarithromycin and erythromycin as QT-prolonging drugs known to cause TdP and the online database, CredibleMeds, that maintains a list of drugs known to cause QT prolongation classifies these drugs as having an increased risk of QT prolongation. The mechanism of this risk has been delineated to involve macrolide binding to and a blockade of delayed rectifier potassium channels that conduct rapid potassium current, I_kr, during repolarization, leading to prolonged repolarization and subsequent QT prolongation. Studies investigating this association have revealed variable results, with several suggesting that the risk of QT prolongation and TdP with macrolide use may be highly dependent on underlying patient risk factors and comorbidities. In the present investigation, we summarize current evidence on association of macrolide antibiotics, azithromycin, clarithromycin and erythromycin, with the development of QT prolongation and TdP, pathophysiology of and risk factors predisposing to development of these events, the role of implementation of strategies to reduce this risk and highlight emerging research. Full article

Background: Prolongation of the QT interval is directly related to the risk of ventricular arrhythmias and sudden cardiac death. Age, comorbidities, and treatment schemes have been shown to influence its prolongation and may also significantly affect the course of SARS-CoV-2 infection. Fluoroquinolones, widely used during the COVID-19 pandemic, are known for their ability to prolong the QT interval. Risk of ventricular arrhythmias has also been reported in patients with infectious diseases, and this risk may have been associated with high levels of interleukin-6 (IL-6). Purpose: The aim of this study is to evaluate the effect of levofloxacin on the corrected QT interval in patients with COVID-19, as well as to identify sociodemographic, clinical, and biochemical parameters associated with QTc interval prolongation among patients with COVID-19. Patients and Methods: The medical records of 93 patients hospitalized for COVID-19 were retrospectively analyzed, focusing on the presence of comorbidities and treatment with levofloxacin. Selected sociodemographic, clinical, and biochemical parameters were then statistically analyzed, with emphasis on their effect on the corrected QTc interval. The QTc interval was calculated according to the Bazett formula. Results: Levofloxacin use was not significantly associated with QTc interval. Statistical analysis identified creatinine, heart failure and atrial fibrillation as significant predictors of QTc interval prolongation. The trends towards QTc interval prolongation observed with hypokalaemia and hypertension suggest that these factors may also contribute to QTc interval variability and should be taken into account when assessing arrhythmia risk. Conclusions: Our retrospective study indicates that QTc prolongation results from the interplay of multiple factors. Full article

Background: Fluoroquinolones, available in topical and oral formulations, are used to manage bacterial skin and soft tissue infections, including Pseudomonas aeruginosa, atypical mycobacteria, and select multidrug-resistant Gram-negative organisms. Their excellent tissue penetration, bactericidal activity, and convenient dosing make them effective for certain skin and soft tissue infections. However, their use is limited by potential safety concerns, including tendinopathy (odds ratio up to 9.1 in corticosteroid users), QT interval prolongation with risk of torsades de pointes, phototoxicity, and rising antimicrobial resistance. Methods: A literature search of PubMed, Scopus, and Web of Science was conducted for articles from January 1985 to April 2025 with the search terms (quinolone OR fluoroquinolone) AND (dermatology OR “skin and soft tissue infection” OR “skin structure infection”). Abstracts and presentations were excluded. A Google search used the same terms for articles from government regulatory agencies. Results: This review provides practical guidance on the clinical use of topical and oral fluoroquinolones in dermatology. Delafloxacin demonstrated over 90% cure rates in trials for complicated skin infections. However, serious safety concerns remain, including a ninefold increase in tendinopathy risk among older adults on corticosteroids and corrected QT intervals exceeding 500 milliseconds in high-risk patients. Phototoxicity varies, with agents like sparfloxacin linked to heightened ultraviolet sensitivity. Resistance to ciprofloxacin exceeds 20 percent in Escherichia coli and P. aeruginosa in some populations. Culture-based prescribing, shorter treatment courses, and preference for topical treatments can reduce risk and preserve efficacy. Conclusions: Fluoroquinolones remain clinically useful in dermatology when prescribed selectively. Their appropriate use requires careful attention to patient risk factors along with their evolving resistance patterns and ongoing stewardship efforts. Full article

Introduction: The combination of BRAF and MEK inhibitors (BRAF/MEKi) has significantly improved survival in melanoma patients with BRAF V600 mutations. However, these agents can cause cardiovascular (CV) toxicity, compromising efficacy. This study evaluated the CV adverse events (cAEs) associated with BRAF/MEKi using the U.S. FDA Adverse Event Reporting System (FAERS) to identify new signals of disproportionate reporting (SDRs). Methods: Descriptive and disproportionality analyses were conducted on reports listing dabrafenib (D), vemurafenib (V), encorafenib (E), trametinib (T), cobimetinib (C), or binimetinib (B) as suspects in monotherapy or combination therapy (D + T, V + C, E + B), with melanoma as the indication and at least one cAE. Standardized MedDRA Queries (SMQs) related to cAEs, including bradyarrhythmias and tachyarrhythmias, cardiac failure, cardiomyopathy, thrombotic events, ischaemic heart disease, and myocarditis/pericarditis, were analyzed. Results: Of the 14,077,067 reports retrieved, 18,370 (0.1%) were linked to BRAF/MEKi, with 1591 (8.7%) reporting cAEs, primarily in combination therapy (n = 1268). Disproportionality analysis identified 64 clinically relevant SDRs, most of which were unexpected. Notable findings included bradyarrhythmias, such as QT prolongation with D + T (n = 59; Reporting Odds Ratio, ROR = 5.09, 95% Confidence Interval, CI = 3.94–6.58), cardiac failure with V + C (29; 3.76, 2.6–5.42), and tachyarrhythmias, particularly atrial fibrillation with D + T (99; 2.37, 1.94–2.89). Among embolic and thrombotic events, clinically significant SDRs were observed for disseminated intravascular coagulation with D + T (38; 10.22, 7.42–14.06) and pulmonary embolism with V + C (22; 2.79, 1.83–4.24). Conclusions: Our findings underscore the need for comprehensive CV monitoring in patients receiving BRAF/MEKi therapy to prevent or detect cAEs early and reduce treatment-related risks, particularly in high-risk populations. Full article

Background and Objectives: Post-term pregnancies are associated with increased risks of perinatal complications. This study aimed to evaluate potential cardiac electrophysiological changes in pregnant women by comparing the QRS duration, interval of corrected QT (QTc), and frontal QRS-T angle [f(QRS-T)] between term and post-term pregnancies. Materials and Methods: In this observational prospective study, 120 pregnant women were enrolled—60 term (37–41 weeks) and 60 post-term (≥42 weeks). All participants underwent standard 12-lead electrocardiography (ECG) and caesarean section with spinal anaesthesia. The QTc interval, QRS duration, and frontal QRS-T angle were measured. Demographic parameters such as age, gestational week, height, and weight were recorded. The SPSS software was used to analyse the data with p < 0.05 as the threshold for significance. Results: Post-operative QTc interval (417.3 ± 20.5 vs. 410.2 ± 14.5, p = 0.032) and f(QRS-T) (28 [16–55] vs. 22 [14–34], p = 0.042) were significantly higher in the post-term group than in the term group. When the change in the f(QRS-T) angle was analysed, there was a significant widening of this angle in the post-term group (from 21 [11–37] to 28 [16–55], p = 0.002). The increased f(QRS-T) angle reflects greater heterogeneity in ventricular depolarisation and repolarisation, which may indicate sub-clinical myocardial stress or altered autonomic regulation in the post-term period. Although no overt arrhythmias were observed, subtle changes in P-wave morphology and QT dispersion were more prevalent in the post-term group. Conclusions: Prolonged QRS duration and an increased f(QRS-T) angle in post-term pregnancies can reflect the underlying changes in cardiac electrophysiology related to prolonged gestation. These ECG parameters may serve as non-invasive indicators of sub-clinical cardiac stress, which could be relevant for anaesthetic risk assessment and perinatal management. Full article

Background: The two antiepileptic drugs lacosamide and lamotrigine exert their antiepileptic effect by inhibiting sodium channels. Lacosamide enhances the inactivation of sodium channels, while lamotrigine inhibits the activation of the channel. Interactions with sodium channels also play an interesting role in cardiac pro- and antiarrhythmia, with inhibition of inactivation, in particular, being regarded as potentially proarrhythmic. Therefore, the ventricular electrophysiologic effects of lacosamide and lamotrigine were investigated in an established experimental whole-heart model. Methods: A total of 67 rabbit hearts were allocated to four groups. Retrograde aortic perfusion was performed using the Langendorff setup. The action potential duration at 90% repolarization (APD₉₀), QT intervals, spatial dispersion of repolarization, effective refractory period, post-repolarization refractoriness, and VT incidence were determined. The electrophysiological effects of lacosamide and lamotrigine were investigated in increasing concentrations on the natively perfused heart. On the other hand, perfusion with the I_Kr-blocker sotalol was performed to increase arrhythmia susceptibility, followed by perfusion with lacosamide or lamotrigine to investigate the effects of both in a setting of increased arrhythmia susceptibility. Perfusion with lacosamide and lamotrigine tended to decrease APD₉₀ and QT-interval. As expected, perfusion with sotalol led to a significant increase in APD₉₀, QT interval, and arrhythmia incidence. Additive perfusion with lacosamide led to a further increase in arrhythmia incidence, while additive perfusion with lamotrigine led to a decrease in VT incidence. Conclusions: In this model, lacosamide showed proarrhythmic effects, especially in the setting of an additive prolonged QT interval. Lamotrigine showed no significant proarrhythmia under baseline conditions and rather antiarrhythmic effects with additive QT prolongation. Full article

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease associated with significant morbidity, including cardiovascular complications. This study investigates the relationship between NAFLD and electrocardiographic parameters indicative of ventricular arrhythmia risk. Materials and Methods: We conducted a cross-sectional study enrolling 136 patients with NAFLD and 136 healthy controls. Electrocardiographic parameters—Tp-e interval, QT and corrected QT (QTc) intervals, and Tp-e/QTc ratio—were measured and compared between groups. Results: Patients with NAFLD exhibited significantly higher Tp-e, QTc, Tp-e/QT ratio, and Tp-e/QTc ratio (p < 0.001, for all) than controls. Subgroup analysis showed progressive increases in Tp-e and Tp-e/QT ratio correlating with NAFLD severity (p < 0.001 and p = 0.001, respectively, for grade 1 vs. grade 2; p < 0.001 and p = 0.001, respectively, for grade 1 vs. grade 3). ROC analysis indicated that the Tp-e interval was a strong predictor for identifying grade 2 or more NAFLD (AUC 0.887, p < 0.001). Conclusions: Our findings highlight the association of NAFLD with prolonged electrocardiographic intervals that may predispose patients to ventricular arrhythmias. These parameters can serve as valuable markers for cardiac risk stratification in patients with NAFLD, suggesting the need for vigilant cardiac follow-up in this population. Full article

Congenital long QT syndrome (LQTS) is a group of heritable conditions that are associated with cardiac repolarization abnormalities characterized by QT prolongation on electrocardiogram and the risk of life-threatening arrhythmias. The prenatal detection of LQTS presents significant challenges for clinicians, and a multidisciplinary approach is required for optimal prenatal and postnatal management. In this comprehensive literature review, we describe strategies for the fetal diagnosis of LQTS with variable initial presentation, genetic testing in suspected fetal LQTS, the utility of fetal magnetocardiography as an additional diagnostic tool, prenatal management, and postnatal treatment. We focus on a multidisciplinary team approach including fetal cardiology, adult and pediatric electrophysiology, neonatology, maternal–fetal medicine, and genetic counselors, all playing vital roles in the comprehensive prenatal management and orchestration of postnatal treatment to optimize neonatal outcomes. Full article