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Heart Rhythm Jun 2024The electromechanical window (EMW) is calculated by subtracting the repolarization duration from a mechanical reference representing contraction duration in the same... (Review)
Review
The electromechanical window (EMW) is calculated by subtracting the repolarization duration from a mechanical reference representing contraction duration in the same heartbeat (e.g., aortic-valve closure during echocardiography with simultaneous ECG). Here, we review the current knowledge on the role of the EMW as an independent parameter for ventricular arrhythmia-risk stratification. We (1) provide a standardized approach to echocardiographic EMW assessment, (2) define relevant cut-off values for both abnormal EMW negativity and positivity, (3) discuss pathophysiologic underpinnings of EMW negativity, and (4) outline the potential future role of cardiac electromechanical relations in patients with proarrhythmic conditions.
PubMed: 38878938
DOI: 10.1016/j.hrthm.2024.06.012 -
The Journal of Biological Chemistry Jun 2024The voltage-gated potassium ion channel K11.1 plays a critical role in cardiac repolarization. Genetic variants that render Kv11.1 dysfunctional cause Long QT Syndrome...
The voltage-gated potassium ion channel K11.1 plays a critical role in cardiac repolarization. Genetic variants that render Kv11.1 dysfunctional cause Long QT Syndrome (LQTS), which is associated with fatal arrhythmias. Approximately 90% of LQTS-associated variants cause intracellular protein transport (trafficking) dysfunction, which pharmacological chaperones like E-4031 can rescue. Protein folding and trafficking decisions are regulated by chaperones, protein quality control factors, and trafficking machinery comprising the cellular proteostasis network. Here, we test whether trafficking dysfunction is associated with alterations in the proteostasis network of pathogenic Kv11.1 variants and whether pharmacological chaperones can normalize the proteostasis network of responsive variants. We used affinity-purification coupled with tandem mass tag-based quantitative mass spectrometry to assess protein interaction changes of wild-type (WT) K11.1 or trafficking-deficient channel variants in the presence or absence of E4031. We identified 572 core K11.1 protein interactors. Trafficking-deficient variants K11.1-G601S and K11.1-G601S-G965* had significantly increased interactions with proteins responsible for folding, trafficking, and degradation compared to WT. We confirmed previous findings that the proteasome is critical for K11.1 degradation. Our report provides the first comprehensive characterization of protein quality control mechanisms of K11.1. We find extensive interactome remodeling associated with trafficking-deficient K11.1 variants, and with pharmacological chaperone rescue of K11.1 cell surface expression. The identified protein interactions could be targeted therapeutically to improve K11.1 trafficking and treat Long QT Syndrome.
PubMed: 38876300
DOI: 10.1016/j.jbc.2024.107465 -
Medicine Jun 2024Using bibliometric analysis, this study attempted to provide an overview of the current state of research and key findings regarding the relationship between atrial... (Observational Study)
Observational Study
Using bibliometric analysis, this study attempted to provide an overview of the current state of research and key findings regarding the relationship between atrial fibrillation (AF) and cryoballoons in general. We gathered the literature from the Web of Science (WOS) database covering the last 11 years (2013-2024) pertaining to AF and cryoballoons, and we used Citespace to evaluate the mapping of knowledge. The findings demonstrated that there were 1986 articles concerning AF and cryoballoons, with a faster growth after 2018. The United States, Vrije Universiteit Brussel, and Chierchia, Gian-Battista are the nation, organization, and writer with the highest number of publications. Kuck KH (2016) is the most frequently mentioned reference as well (488). We know that Vrije Universiteit Brusse in the Belgium has emerged as 1 of this discipline's leading research forces based on a 10-year bibliometric investigation. Prominent universities and developed nations form the finest alliances for research on cryoballoons and AF.
Topics: Atrial Fibrillation; Bibliometrics; Humans; Cryosurgery; Biomedical Research
PubMed: 38875388
DOI: 10.1097/MD.0000000000038435 -
Medicine Jun 2024Bone cement implantation syndrome (BCIS) is a critical and potentially life-threatening condition that manifests during implantation. Characterized by a constellation of... (Review)
Review
Bone cement implantation syndrome (BCIS) is a critical and potentially life-threatening condition that manifests during implantation. Characterized by a constellation of symptoms, including hypoxemia, hypotension, cardiac arrhythmias, elevated pulmonary vascular resistance, and occasionally cardiac arrest, BCIS typically ensues shortly after cement introduction, albeit with rare instances of delayed onset. Primarily attributed to the exothermic reaction of bone cement implantation, this syndrome is caused by local tissue damage, histamine and prostaglandin release, and microemboli formation, ultimately triggering a systemic immune response that culminates in respiratory and circulatory failure. The current hypotheses regarding BCIS include embolism, allergic reactions, and cement autotoxicity. BCIS management emphasizes preventative strategies, encompassing meticulous patient risk assessment, comprehensive preoperative and intraoperative evaluations, and precise cement application techniques. Treatment primarily involves symptomatic therapy and life-support measures to address the systemic effects of the syndrome.
Topics: Humans; Bone Cements; Syndrome; Postoperative Complications
PubMed: 38875363
DOI: 10.1097/MD.0000000000038624 -
Clinical Cardiology Jun 2024The ambulatory arterial stiffness index (AASI) is an indirect measure of blood pressure variability and arterial stiffness which are atrial fibrillation (AF) risk... (Observational Study)
Observational Study
BACKGROUND
The ambulatory arterial stiffness index (AASI) is an indirect measure of blood pressure variability and arterial stiffness which are atrial fibrillation (AF) risk factors. The relationship between AASI and AF development has not been previously investigated and was the primary aim of this study.
METHODS
This was an observational cohort study of adults (aged 18-85 years) in sinus rhythm, who underwent 24-h ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension or its control.
RESULTS
Eight hundred and twenty-one patients (49% men) aged 58.7 ± 15.3 years were followed up for a median of 4.0 years (3317 patient-years). In total, 75 patients (9.1%) developed ≥1 AF episode during follow-up. The mean AASI was 0.46 ± 0.17 (median 0.46). AASI values (0.52 ± 0.16 vs. 0.45 ± 0.17; p < .001) and the proportion of AASI values above the median (65.3% vs. 48.4%; p = .005) were greater among the patients who developed AF versus those that did not respectively. AASI significantly correlated with age (r = .49; 95% confidence interval: 0.44-0.54: p < .001). On Kaplan-Meier analysis, higher baseline AASI by median, tertiles, and quartiles were all significantly associated with AF development (X: 10.13; p < .001). On Cox regression analyses, both a 1-standard deviation increase and AASI > median were independent predictors of AF, but this relationship was no longer significant when age was included in the model.
CONCLUSIONS
AASI is an independent predictor of AF development. However, this relationship becomes insignificant after adjustment for age which is higher correlated with AASI.
Topics: Humans; Atrial Fibrillation; Middle Aged; Male; Female; Aged; Adult; Blood Pressure Monitoring, Ambulatory; Vascular Stiffness; Risk Factors; Aged, 80 and over; Adolescent; Incidence; Young Adult; Hypertension; Blood Pressure; Risk Assessment; Time Factors; Predictive Value of Tests; Follow-Up Studies; Retrospective Studies
PubMed: 38873860
DOI: 10.1002/clc.24299 -
Current Treatment Options in... Dec 2023Sudden cardiac arrest is associated with high morbidity and mortality. Despite having a disproportionate burden of sudden cardiac death (SCD), rates of primary and...
PURPOSE OF REVIEW
Sudden cardiac arrest is associated with high morbidity and mortality. Despite having a disproportionate burden of sudden cardiac death (SCD), rates of primary and secondary prevention of SCD with implantable cardioverter-defibrillator (ICD) therapy are lower among eligible racially minoritized patients. This review highlights the racial and ethnic disparities in ICD utilization, associated barriers to ICD care, and proposed interventions to improve equitable ICD uptake.
RECENT FINDINGS
Racially minoritized populations are disproportionately eligible for ICD therapy but are less likely to see cardiac specialists, be counseled on ICD therapy, and ultimately undergo ICD implantation, fueling disparate outcomes. Racial disparities in ICD utilization are multifactorial, with contributions at the patient, provider, health system, and structural/societal level.
SUMMARY
Racial and ethnic disparities have been demonstrated in preventing SCD with ICD use. Proposed strategies to mitigate these disparities must prioritize care delivery and access to care for racially minoritized patients, increase the diversification of clinical and implementation trial participants and the healthcare workforce, and center reparative justice frameworks to rectify a long history of racial injustice.
PubMed: 38873495
DOI: 10.1007/s11936-023-01025-z -
Frontiers in Genetics 2024Long QT syndrome (LQTS) is an inherited malignant arrhythmia syndrome that poses a risk of sudden death. Variants in the Potassium Voltage-Gated Channel Subfamily H...
BACKGROUND
Long QT syndrome (LQTS) is an inherited malignant arrhythmia syndrome that poses a risk of sudden death. Variants in the Potassium Voltage-Gated Channel Subfamily H Member 2 () gene are known to cause Long QT syndrome through an autosomal dominant inheritance pattern. However, as of now, there have been no reports of any variant leading to Long QT syndrome exhibiting incomplete penetrance that is influenced by gender.
METHODS
Whole-exome sequencing (WES) was conducted on the proband to identify pathogenic variants. Subsequently, Sanger sequencing was employed to validate the identified likely pathogenic variants in all family members.
RESULTS
We analyzed a pedigree spanning three-generations afflicted by Long QT syndrome. WES revealed a novel missense variant (p.Val630Gly, c.1889 T>G) as the causative factor for the family's phenotype. Within this family, all three male carriers of the variant carriers exhibited the Long QT syndrome phenotype: one experienced sudden death during sleep, another received an implantable cardioverter defibrillator (ICD), and a younger man displayed a prolonged QTc interval without any instances of syncope or malignant arrhythmia to date. Interestingly, the middle-aged female carrier showed no Long QT Syndrome phenotype. However, her offspring, diagnosed with Turner syndrome (45, X) and also a carrier of this variant, experienced frequent syncope starting at 12 years old and was diagnosed with Long QT syndrome, leading to an ICD implantation when she was 15 years old. These observations suggest that the manifestation of Long QT syndrome associated with this KCNH2 variant exhibits incomplete penetrance influenced by gender within this family, indicating potential protective mechanisms against the syndrome in females affected by this variant.
CONCLUSION
Our investigation has led to the identification of a novel pathogenic variant responsible for Long QT syndrome within a familial context characterized by gender-selective, incomplete penetrance. This discovery highlights a unique pathogenic inheritance pattern for the gene associated with Long QT syndrome, and could potentially shed light on the distinct penetrance behaviors and patterns of the gene. This discovery broadens our exploration of the KCNH2 gene in cardiac arrhythmias, highlighting the intricate genetic dynamics behind Long QT syndrome.
PubMed: 38873110
DOI: 10.3389/fgene.2024.1409459 -
Etomidate-induced hypokalemia in electronic cigarette users: two case reports and literature review.Frontiers in Endocrinology 2024Hypokalemia is a common clinical condition that can lead to muscle weakness, difficulty breathing, malignant arrhythmias, and even death. This report describes two cases... (Review)
Review
Hypokalemia is a common clinical condition that can lead to muscle weakness, difficulty breathing, malignant arrhythmias, and even death. This report describes two cases of severe hypokalemia resulting from the use of electronic cigarettes containing etomidate, both accompanied by varying degrees of adrenal hyperplasia. In both cases, the patients were admitted to the hospital with lower limb weakness and difficulty walking. Relevant examinations revealed low blood potassium, low cortisol, high adrenocorticotropic hormone, low renin, and low aldosterone levels in the patients, with Case 2 also having significant hypertension. In both cases, adrenal CT scans showed thickening of the adrenal glands. After the delivery of potassium supplementation in both cases, blood potassium levels gradually returned to normal and muscle strength gradually improved. The case reports are followed by a review of the literature on etomidate and its related mechanisms of action with discussion of its association with hypokalemia.
Topics: Adult; Humans; Male; Electronic Nicotine Delivery Systems; Etomidate; Hypokalemia
PubMed: 38872965
DOI: 10.3389/fendo.2024.1321610 -
Physiological Reports Jun 2024We aimed to determine the relative contribution of hypercapnia and hypoxia to the bradycardic response to apneas. We hypothesized that apneas with hypercapnia would...
We aimed to determine the relative contribution of hypercapnia and hypoxia to the bradycardic response to apneas. We hypothesized that apneas with hypercapnia would cause greater bradycardia than normoxia, similar to the response seen with hypoxia, and that apneas with hypercapnic hypoxia would induce greater bradycardia than hypoxia or hypercapnia alone. Twenty-six healthy participants (12 females; 23 ± 2 years; BMI 24 ± 3 kg/m) underwent three gas challenges: hypercapnia (+5 torr end tidal partial pressure of CO [PCO]), hypoxia (50 torr end tidal partial pressure of O [PO]), and hypercapnic hypoxia (combined hypercapnia and hypoxia), with each condition interspersed with normocapnic normoxia. Heart rate and rhythm, blood pressure, PCO, PO, and oxygen saturation were measured continuously. Hypercapnic hypoxic apneas induced larger bradycardia (-19 ± 16 bpm) than normocapnic normoxic apneas (-11 ± 15 bpm; p = 0.002), but had a comparable response to hypoxic (-19 ± 15 bpm; p = 0.999) and hypercapnic apneas (-14 ± 14 bpm; p = 0.059). Hypercapnic apneas were not different from normocapnic normoxic apneas (p = 0.134). After removal of the normocapnic normoxic heart rate response, the change in heart rate during hypercapnic hypoxia (-11 ± 16 bpm) was similar to the summed change during hypercapnia+hypoxia (-9 ± 10 bpm; p = 0.485). Only hypoxia contributed to this bradycardic response. Under apneic conditions, the cardiac response is driven by hypoxia.
Topics: Humans; Hypercapnia; Female; Male; Heart Rate; Hypoxia; Apnea; Adult; Bradycardia; Young Adult; Blood Pressure; Carbon Dioxide
PubMed: 38872580
DOI: 10.14814/phy2.16054 -
Mathematical Biosciences and... May 2024Within the domain of cardiovascular diseases, arrhythmia is one of the leading anomalies causing sudden deaths. These anomalies, including arrhythmia, are detectable...
Within the domain of cardiovascular diseases, arrhythmia is one of the leading anomalies causing sudden deaths. These anomalies, including arrhythmia, are detectable through the electrocardiogram, a pivotal component in the analysis of heart diseases. However, conventional methods like electrocardiography encounter challenges such as subjective analysis and limited monitoring duration. In this work, a novel hybrid model, AttBiLFNet, was proposed for precise arrhythmia detection in ECG signals, including imbalanced class distributions. AttBiLFNet integrates a Bidirectional Long Short-Term Memory (BiLSTM) network with a convolutional neural network (CNN) and incorporates an attention mechanism using the focal loss function. This architecture is capable of autonomously extracting features by harnessing BiLSTM's bidirectional information flow, which proves advantageous in capturing long-range dependencies. The attention mechanism enhances the model's focus on pertinent segments of the input sequence, which is particularly beneficial in class imbalance classification scenarios where minority class samples tend to be overshadowed. The focal loss function effectively addresses the impact of class imbalance, thereby improving overall classification performance. The proposed AttBiLFNet model achieved 99.55% accuracy and 98.52% precision. Moreover, performance metrics such as MF1, K score, and sensitivity were calculated, and the model was compared with various methods in the literature. Empirical evidence showed that AttBiLFNet outperformed other methods in terms of both accuracy and computational efficiency. The introduced model serves as a reliable tool for the timely identification of arrhythmias.
Topics: Humans; Arrhythmias, Cardiac; Electrocardiography; Neural Networks, Computer; Algorithms; Signal Processing, Computer-Assisted; Reproducibility of Results
PubMed: 38872562
DOI: 10.3934/mbe.2024259