The ion channel basis of pharmacological effects of amiodarone on myocardial electrophysiological properties, a comprehensive review.

Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III antiarrhythmic drugs is the cardiac human ether-a-go-go-related gene (hERG) encoded channel, KCNH2, commonly known as HERG, that conducts the rapidly activating delayed rectifier potassium current (IKr). Like other class III antiarrhythmic drugs, amiodarone exerts its physiologic effects mainly through IKr blockade, delaying the repolarization phase of the action potential and extending the effective refractory period. However, while many class III antiarrhythmics, including sotalol and dofetilide, can cause long QT syndrome (LQTS) that can progress to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia. This review article discusses the arrhythmogenesis in LQTS from the aspects of the development of early afterdepolarizations (EADs) associated with Ca2+ current, transmural dispersion of repolarization (TDR), as well as reverse use dependence associated with class III antiarrhythmic drugs to highlight electropharmacological effects of amiodarone on the myocardium.

Impact of an online course on enhancing the diagnosis of Chagas disease in Latin America.

Objective: Chagas disease poses a public health problem in Latin America, and the electrocardiogram is a crucial tool in the diagnosis and monitoring of this pathology. In this context, the aim of this study was to quantify the change in the ability to detect electrocardiographic patterns among healthcare professionals after completing a virtual course. Materials and Methods: An asynchronous virtual course with seven pre-recorded classes was conducted. Participants answered the same questionnaire at the beginning and end of the training. Based on these responses, pre and post-test results for each participant were compared. Results: The study included 1656 participants from 21 countries; 87.9% were physicians, 5.2% nurses, 4.1% technicians, and 2.8% medical students. Initially, 3.1% answered at least 50% of the pre-test questions correctly, a proportion that increased to 50.4% after the course (p=0.001). Regardless of their baseline characteristics, 82.1% of course attendees improved their answers after completing the course. Conclusions: The implementation of an asynchronous online course on electrocardiography in Chagas disease enhanced the skills of both medical and non-medical personnel to recognize this condition.

Pattern Recognition and Inductive-Deductive Reasoning: Two Cornerstones of Electrocardiogram Teaching.

Almost half of physicians report being uncomfortable with ECG interpretation, underscoring the need for high-quality ECG training. There are two major strategies for teaching ECG interpretation. Pattern recognition involves reading ECGs solely as graphic images, after being taught the underlying pathophysiology behind the ECG patterns. Inductive-deductive reasoning requires logical thought mechanisms, using clinical context and algorithms, to reach a correct diagnosis. It is important for ECG educators to choose between these teaching strategies, depending on the clinical scenario. Hopefully, consistency around teaching strategies will help learners to become more comfortable in ECG interpretation, and ultimately correctly interpret ECGs more frequently.

Original algorithms for the detection of cardiovascular involvement of neglected tropical diseases.

INTRODUCTION: Neglected tropical diseases (NTDs) introduce considerable morbidity and mortality on a global scale, directly impacting over 1 billion individuals as well as their families and communities. Afflicted individuals may have limited access to resources and care in these regions, contributing to a high proportion of chronic, progressive, and systemic disease. The cardiovascular system is at particular risk of demise for several NTDs, yet remains largely unstudied due in part to the lack of robust data collection mechanisms in the most impacted regions. AREAS COVERED: The present review is a part of the Neglected Tropical Diseases and other Infectious Diseases affecting the Heart (NET-Heart) Project, aiming at summarizing the current knowledge on cardiovascular implications of NTDs and providing diagnostic as well as management recommendations which can be tailored to low-resource settings. The diagnostic and management algorithms of 13 unique NTDs are presented and summarized. EXPERT OPINION: Recognizing cardiac manifestations of NTDs can significantly alter disease trajectory and all physicians benefit from improved knowledge about NTDs. Great potential exists to advance patient care by improving data collection, communication, and international collaboration.

Animal models of Lyme carditis. Understanding how to study a complex disease.

Lyme carditis, a well-established manifestation of Lyme disease, has been studied in animal models to improve understanding of its pathogenesis. This review synthesizes existing literature on these models and associated disease mechanisms. Searches in MEDLINE, Embase, BIOSIS, and Web of Science yielded 53 articles (47 mice models and 6 other animal models). Key findings include: 1) Onset of carditis correlates with spirochete localization in the heart; 2) Carditis occurs within 10 days of infection, progressing to peak inflammation within 30 days; 3) Infiltrates were predominantly composed of Mac-1+ macrophages and were associated with increases in TNF-α, IL-1 and IL-12 cytokines; 4) Resolution of inflammation was primarily mediated by lymphocytes; 5) Immune system is a double-edged sword: it can play a role in the progression and severity of carditis, but can also have a protective effect. Animal models offer valuable insights into the evolution and pathophysiologic mechanisms of Lyme carditis.

PR prolongation as a predictor of atrial fibrillation onset: A state-of-the-art review.

First-degree atrioventricular block (1-AVB), characterized by a PR interval exceeding 200 milliseconds, has traditionally been perceived as a benign cardiac condition. Recently, this perception has been challenged by investigations that indicate a potential association between PR prolongation and an elevated risk of atrial fibrillation (AF). To consolidate these findings, we performed a comprehensive review to assess the available evidence indicating a relationship between these two conditions. We searched MEDLINE and EMBASE databases as well as manually searched references of retrieved articles. We selected 18 cohort studies/meta-analyses involving general and special populations. Consistent findings across expansive cohort studies reveal that incremental increases in the PR interval may serve as an independent risk factor for AF. However, our analyses underscore the need for further research into the association between 1-AVB, defined by a specified PR interval cutoff, and the risk of AF.

Review of Athletic Guidelines for High-Altitude Training and Acclimatization.

Ramchandani, Rashi, Ioana Tereza Florica, Zier Zhou, Aziz Alemi, and Adrian Baranchuk. Review of athletic guidelines for high-altitude training and acclimatization. High Alt Med Biol. 00:000-000, 2024. Introduction: Exposure to high altitude results in hypobaric hypoxia with physiological acclimatization changes that are thought to influence athletic performance. This review summarizes existing literature regarding implications of high-altitude training and altitude-related guidelines from major governing bodies of sports. Methods: A nonsystematic review was performed using PubMed and OVID Medline to identify articles regarding altitude training and guidelines from international governing bodies of various sports. Sports inherently involving training or competing at high altitude were excluded. Results: Important physiological compensatory mechanisms to high-altitude environments include elevations in blood pressure, heart rate, red blood cell mass, tidal volume, and respiratory rate. These responses can have varying effects on athletic performance. Governing sport bodies have limited and differing regulations for training and competition at high altitudes with recommended acclimatization periods ranging from 3 days to 3 weeks. Discussion: Physiological changes in response to high terrestrial altitude exposure can have substantial impacts on athletic performance. Major sport governing bodies have limited regulations and recommendations regarding altitude training and competition. Existing guidelines are variable and lack substantial evidence to support recommendations. Additional studies are needed to clarify the implications of high-altitude exposure on athletic ability to optimize training and competition.

EDUCATE: An international, randomized controlled trial for teaching electrocardiography.

INTRODUCTION: Despite the critical role of electrocardiograms (ECGs) in patient care, evident gaps exist in ECG interpretation competency among healthcare professionals across various medical disciplines and training levels. Currently, no practical, evidence-based, and easily accessible ECG learning solution is available for healthcare professionals. The aim of this study was to assess the effectiveness of web-based, learner-directed interventions in improving ECG interpretation skills in a diverse group of healthcare professionals. METHODS: In an international, prospective, randomized controlled trial, 1206 healthcare professionals from various disciplines and training levels were enrolled. They underwent a pre-intervention test featuring 30 12-lead ECGs with common urgent and non-urgent findings. Participants were randomly assigned to four groups: (i) practice ECG interpretation question bank (question bank), (ii) lecture-based learning resource (lectures), (iii) hybrid question- and lecture-based learning resource (hybrid), or (iv) no ECG learning resources (control). After four months, a post-intervention test was administered. The primary outcome was the overall change in ECG interpretation performance, with secondary outcomes including changes in interpretation time, self-reported confidence, and accuracy for specific ECG findings. Both unadjusted and adjusted scores were used for performance assessment. RESULTS: Among 1206 participants, 863 (72 %) completed the trial. Following the intervention, the question bank, lectures, and hybrid intervention groups each exhibited significant improvements, with average unadjusted score increases of 11.4 % (95 % CI, 9.1 to 13.7; P<0.01), 9.8 % (95 % CI, 7.8 to 11.9; P<0.01), and 11.0 % (95 % CI, 9.2 to 12.9; P<0.01), respectively. In contrast, the control group demonstrated a non-significant improvement of 0.8 % (95 % CI, -1.2 to 2.8; P=0.54). While no differences were observed among intervention groups, all outperformed the control group significantly (P<0.01). Intervention groups also excelled in adjusted scores, confidence, and proficiency for specific ECG findings. CONCLUSION: Web-based, self-directed interventions markedly enhanced ECG interpretation skills across a diverse range of healthcare professionals, providing an accessible and evidence-based solution.

Violence and aggression against nurses during the COVID-19 pandemic in Latin America. From the emerging leaders program of the Interamerican Society of Cardiology (SIAC).

INTRODUCTION: During the Coronavirus (COVID-19) pandemic, healthcare providers have overcome difficult experiences such as workplace violence. Nurses are particularly vulnerable to workplace violence. The objective of this study was to characterize violence and aggression against nurses during the COVID-19 pandemic in Latin America. METHODS: An electronic cross-sectional survey was conducted in 19 Latin American countries to characterize the frequency and type of violent actions against front-line healthcare providers. RESULTS: Of the original 3544 respondents, 16% were nurses (n = 567). The mean age was 39.7 ± 9.0 years and 79.6% (n = 2821) were women. In total, 69.8% (n = 2474) worked in public hospitals and 81.1% (n = 2874) reported working regularly with COVID-19 patients. Overall, about 68.6% (n = 2431) of nurses experienced at least one episode of workplace aggression during the pandemic. Nurses experienced weekly aggressions more frequently than other healthcare providers (45.5% versus 38.1%, p < .007). Nurses showed a trend of lower reporting rates against the acts of aggression suffered (p = .076). In addition, nurses were more likely to experience negative cognitive symptoms after aggressive acts (33.4% versus 27.8%, p = .028). However, nurses reported considering changing their work tasks less frequently compared to other healthcare providers after an assault event (p = .005). CONCLUSION: Workplace violence has been a frequent problem for all healthcare providers during COVID-19 pandemic in Latin America. Nurses were a particularly vulnerable subgroup, with higher rates of aggressions and cognitive symptoms and lower rate of complaints than other healthcare providers who suffered from workplace violence. It is imperative to develop strategies to protect this vulnerable group from aggressions during their tasks.

Arrhythmias in transgender individuals.

The need to improve access to health services for the transgender community has become evident, especially concerning cardiovascular risk, which is higher compared to the general population. Surgical procedures and hormone therapies are common in this population to affirm gender identity, but they pose challenges as they are associated with disruptions in lipid metabolism, body fat concentration, and insulin resistance. Additionally, there is an increased risk of adverse cardiovascular events such as venous thromboembolism, stroke, and myocardial infarction. The influence of sex hormones on the electrophysiological properties of the heart has been studied, highlighting gender differences that may predispose the transgender population to cardiac arrhythmias. Exogenous hormone therapy, for both transgender women and men, can affect the QT interval and increase the risk of arrhythmias, including atrial fibrillation. Although the incidence of arrhythmias in the transgender population is not entirely clear, evidence suggests the need for careful cardiovascular monitoring and consideration of risk factors before initiating hormone therapies.

La necesidad de mejorar el acceso a servicios de salud para la comunidad transgénero se ha vuelto evidente, especialmente en relación con el riesgo cardiovascular, que es más alto en comparación con la población general. Los procedimientos quirúrgicos y las terapias hormonales son comunes en esta población para reafirmar la identidad de género, pero plantean desafíos, ya que se asocian con alteraciones en el metabolismo de lípidos, la concentración de grasa corporal y la resistencia a la insulina. Además, existe un aumento en el riesgo de eventos cardiovasculares adversos, como tromboembolia venosa, accidente cerebrovascular e infarto de miocardio. La influencia de las hormonas sexuales en las propiedades electrofisiológicas del corazón ha sido estudiada, destacando diferencias entre géneros que pueden predisponer a la población transgénero a arritmias cardiacas. La terapia hormonal exógena, tanto para mujeres como para hombres trans, puede afectar el intervalo QT y aumentar el riesgo de arritmias, incluida la fibrilación auricular. Aunque la incidencia de arritmias en la población transgénero aún no está completamente clara, la evidencia sugiere la necesidad de un monitoreo cardiovascular cuidadoso y la consideración de factores de riesgo antes de iniciar terapias hormonales.

Left bundle branch pacing in alternating bundle branch block.

We present a case of symptomatic intermittent AV block showing during monitorization alternating bundle branch block. Presuming a high need of pacing, conduction system pacing was considered a more physiological alternative in this patient. Left bundle branch pacing restored a stable atrioventricular synchrony with a paced QRS complex similar to the native one and might be a good alternative in these cases.

New pattern of atypical advanced interatrial block.

INTRODUCTION: Interatrial block (IAB) is defined as prolonged P-wave duration (≥ 120 ms) due to delayed conduction in the Bachmann bundle. This is readily identifiable using surface electrocardiogram (ECG). Advanced IAB can be classified as typical and atypical. Atypical IAB can be further categorized by (i) duration or (ii) morphology. In this report, we have identified a new pattern of atypical IAB with triphasic morphology of the P-wave in the inferior leads. METHODS: Two clinical cases were evaluated including surface ECGs. P-wave durations and amplitudes were measured with digital calipers using ECG analysis software (MUSE, GE HealthCare). Comparisons were made using prior data to evaluate IAB and P-wave duration and morphology. RESULTS: A new pattern of atypical advanced IAB shows prolonged P-wave duration (P wave >160 ms) and triphasic morphology in all inferior leads with P +/+/- and P +/-/+, respectively. We speculate that triphasic P-waves in the inferior leads represent three moments of atrial depolarization; from right to left. CONCLUSION: This study describes a novel pattern of atypical advanced IAB. Further investigation regarding the increased risk of atrial fibrillation and stroke associated with this new pattern is warranted in the future.

Predictors of ECG Interpretation Proficiency in Healthcare Professionals.

Accurate ECG interpretation is vital, but variations in skills exist among healthcare professionals. This study aims to identify factors contributing to ECG interpretation proficiency. Survey data and ECG interpretation test scores from participants in the EDUCATE Trial were analyzed to identify predictors of performance for 30 sequential 12-lead ECGs. Nonmodifiable factors (being a physician, clinical experience, patient care impact) and modifiable factors (weekly interpretation volume, training hours, expert supervision frequency) were analyzed. Bivariate and multivariate analyses were used to generate a Comprehensive Model (incorporating all factors) and Actionable Model (incorporating modifiable factors only). Among 1206 participants analyzed, there were 72 (6.0%) primary care physicians, 146 (12.1%) cardiology fellows-in-training, 353 (29.3%) resident physicians, 182 (15.1%) medical students, 84 (7.0%) advanced practice providers, 120 (9.9%) nurses, and 249 (20.7%) allied health professionals. Among them, 571 (47.3%) were physicians and 453 (37.6%) were nonphysicians. The average test score was 56.4% ± 17.2%. Bivariate analysis demonstrated significant associations between test scores and >10 weekly ECG interpretations, being a physician, >5 training hours, patient care impact, and expert supervision but not clinical experience. In the Comprehensive Model, independent associations were found with weekly interpretation volume (9.9 score increase; 95% CI, 7.9-11.8; P < 0.001), being a physician (9.0 score increase; 95% CI, 7.2-10.8; P < 0.001), and training hours (5.7 score increase; 95% CI, 3.7-7.6; P < 0.001). In the Actionable Model, scores were independently associated with weekly interpretation volume (12.0 score increase; 95% CI, 10.0-14.0; P < 0.001) and training hours (4.7 score increase; 95% CI, 2.6-6.7; P < 0.001). The Comprehensive and Actionable Models explained 18.7% and 12.3% of the variance in test scores, respectively. Predictors of ECG interpretation proficiency include nonmodifiable factors like physician status and modifiable factors such as training hours and weekly ECG interpretation volume.

ECG Interpretation Proficiency of Healthcare Professionals.

ECG interpretation is essential in modern medicine, yet achieving and maintaining competency can be challenging for healthcare professionals. Quantifying proficiency gaps can inform educational interventions for addressing these challenges. Medical professionals from diverse disciplines and training levels interpreted 30 12-lead ECGs with common urgent and nonurgent findings. Average accuracy (percentage of correctly identified findings), interpretation time per ECG, and self-reported confidence (rated on a scale of 0 [not confident], 1 [somewhat confident], or 2 [confident]) were evaluated. Among the 1206 participants, there were 72 (6%) primary care physicians (PCPs), 146 (12%) cardiology fellows-in-training (FITs), 353 (29%) resident physicians, 182 (15%) medical students, 84 (7%) advanced practice providers (APPs), 120 (10%) nurses, and 249 (21%) allied health professionals (AHPs). Overall, participants achieved an average overall accuracy of 56.4% ± 17.2%, interpretation time of 142 ± 67 seconds, and confidence of 0.83 ± 0.53. Cardiology FITs demonstrated superior performance across all metrics. PCPs had a higher accuracy compared to nurses and APPs (58.1% vs 46.8% and 50.6%; P < 0.01), but a lower accuracy than resident physicians (58.1% vs 59.7%; P < 0.01). AHPs outperformed nurses and APPs in every metric and showed comparable performance to resident physicians and PCPs. Our findings highlight significant gaps in the ECG interpretation proficiency among healthcare professionals.

Impact of Computer-Interpreted ECGs on the Accuracy of Healthcare Professionals.

The interpretation of electrocardiograms (ECGs) involves a dynamic interplay between computerized ECG interpretation (CEI) software and human overread. However, the impact of computer ECG interpretation on the performance of healthcare professionals remains largely unexplored. The aim of this study was to evaluate the interpretation proficiency of various medical professional groups, with and without access to the CEI report. Healthcare professionals from diverse disciplines, training levels, and countries sequentially interpreted 60 standard 12-lead ECGs, demonstrating both urgent and nonurgent findings. The interpretation process consisted of 2 phases. In the first phase, participants interpreted 30 ECGs with clinical statements. In the second phase, the same 30 ECGs and clinical statements were randomized and accompanied by a CEI report. Diagnostic performance was evaluated based on interpretation accuracy, time per ECG (in seconds [s]), and self-reported confidence (rated 0 [not confident], 1 [somewhat confident], or 2 [confident]). A total of 892 participants from various medical professional groups participated in the study. This cohort included 44 (4.9%) primary care physicians, 123 (13.8%) cardiology fellows-in-training, 259 (29.0%) resident physicians, 137 (15.4%) medical students, 56 (6.3%) advanced practice providers, 82 (9.2%) nurses, and 191 (21.4%) allied health professionals. The inclusion of the CEI was associated with a significant improvement in interpretation accuracy by 15.1% (95% confidence interval, 14.3-16.0; P < 0.001), decrease in interpretation time by 52 s (-56 to -48; P < 0.001), and increase in confidence by 0.06 (0.03-0.09; P = 0.003). Improvement in interpretation accuracy was seen across all professional subgroups, including primary care physicians by 12.9% (9.4-16.3; P = 0.003), cardiology fellows-in-training by 10.9% (9.1-12.7; P < 0.001), resident physicians by 14.4% (13.0-15.8; P < 0.001), medical students by 19.9% (16.8-23.0; P < 0.001), advanced practice providers by 17.1% (13.3-21.0; P < 0.001), nurses by 16.2% (13.4-18.9; P < 0.001), allied health professionals by 15% (13.4-16.6; P < 0.001), physicians by 13.2% (12.2-14.3; P < 0.001), and nonphysicians by 15.6% (14.3-17.0; P < 0.001).CEI integration improves ECG interpretation accuracy, efficiency, and confidence among healthcare professionals.

Differential Effects of Remdesivir and Lumacaftor on Homomeric and Heteromeric hERG Channels.

The human ether-a-go-go-related gene (hERG) encodes for the pore-forming subunit of the channel that conducts the rapidly activating delayed K+ current (IKr) in the heart. The hERG channel is important for cardiac repolarization, and reduction of its expression in the plasma membrane due to mutations causes long QT syndrome type 2 (LQT2). As such, promoting hERG membrane expression is a strategy to rescue mutant channel function. In the present study, we applied patch clamp, western blots, immunocytochemistry, and quantitative reverse transcription polymerase chain reaction techniques to investigate the rescue effects of two drugs, remdesivir and lumacaftor, on trafficking-defective mutant hERG channels. As our group has recently reported that the antiviral drug remdesivir increases wild-type (WT) hERG current and surface expression, we studied the effects of remdesivir on trafficking-defective LQT2-causing hERG mutants G601S and R582C expressed in HEK293 cells. We also investigated the effects of lumacaftor, a drug used to treat cystic fibrosis, that promotes CFTR protein trafficking and has been shown to rescue membrane expression of some hERG mutations. Our results show that neither remdesivir nor lumacaftor rescued the current or cell-surface expression of homomeric mutants G601S and R582C. However, remdesivir decreased while lumacaftor increased the current and cell-surface expression of heteromeric channels formed by WT hERG and mutant G601S or R582C hERG. We concluded that drugs can differentially affect homomeric WT and heteromeric WT+G601S (or WT+R582C) hERG channels. These findings extend our understanding of drug-channel interaction and may have clinical implications for patients with hERG mutations. SIGNIFICANCE STATEMENT: Various naturally occurring mutations in a cardiac potassium channel called hERG can impair channel function by decreasing cell-surface channel expression, resulting in cardiac electrical disturbances and even sudden cardiac death. Promotion of cell-surface expression of mutant hERG channels represents a strategy to rescue channel function. This work demonstrates that drugs such as remdesivir and lumacaftor can differently affect homomeric and heteromeric mutant hERG channels, which have biological and clinical implications.