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PLoS Computational Biology Jun 2024Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed...
Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.
PubMed: 38917196
DOI: 10.1371/journal.pcbi.1012244 -
PloS One 2024Atrial fibrillation is responsible for a considerable number of cases of cardioembolism, accounting for 17% to 30% of the etiologies of all strokes. The software known...
INTRODUCTION
Atrial fibrillation is responsible for a considerable number of cases of cardioembolism, accounting for 17% to 30% of the etiologies of all strokes. The software known as Stroke Risk Analysis (SRA) detects patients at high risk of paroxysmal atrial fibrillation by analyzing a continuous electrocardiogram recorded over different periods of time.
OBJECTIVES
This article aims to carry out a systematic review investigating the effectiveness of the SRA method in predicting the risk of stroke patients having paroxysmal atrial fibrillation as the cause of the event.
METHODS
The methods correspond to the format of the International Prospective Register of Systematic Reviews Protocol, according to CRD Identification Code: CRD42021253974. A systematic search was carried out in BMJB, PubMed/MEDLINE, Science Direct and LILACS. Six cohort studies met the inclusion criteria, representing a total of 2,088 participants with stroke, and compared the detection of patients with paroxysmal atrial fibrillation on the continuous recording electrocardiogram with a time variation of 1 to 48h with the use of SRA.
RESULTS
Studies have shown that SRA has a high negative predictive value (between 96 and 99.1%) and can contribute to the selection of patients at high risk of paroxysmal atrial fibrillation to be referred for implantable cardiac monitoring to continue the investigation.
CONCLUSIONS
A sequential combination of SRA with implantable cardiac monitoring is a promising strategy for detecting undiagnosed paroxysmal atrial fibrillation. Thus, the SRA can act as a cost-effective pre-selection tool to identify patients at higher risk of having paroxysmal atrial fibrillation as a possible cause of stroke and who may benefit from implantable cardiac monitoring. However, the lack of randomized studies is a limitation that must be considered.
Topics: Atrial Fibrillation; Humans; Stroke; Risk Assessment; Electrocardiography; Risk Factors
PubMed: 38917112
DOI: 10.1371/journal.pone.0305339 -
Frontiers in Cardiovascular Medicine 2024Data on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce.
Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: the ASPIRE (efficAcy and safety of aPixaban in rEal-world practice in Korean frail patients with atrial fibrillation) study.
BACKGROUND
Data on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce.
OBJECTIVES
We prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion.
METHODS
The multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose.
RESULTS
Of 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the "marginal zone," defined as age 75-80 years, weight 60-65 kg, and creatinine levels 1.2-1.5 mg/dL.
CONCLUSIONS
In real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.
PubMed: 38915744
DOI: 10.3389/fcvm.2024.1367623 -
Journal of Korean Medical Science Jun 2024Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond...
BACKGROUND
Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using real-world data.
METHODS
Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke.
RESULTS
Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62-0.97; = 0.024).
CONCLUSION
As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.
Topics: Humans; Atrial Fibrillation; Male; Female; Aged; Middle Aged; Platelet Aggregation Inhibitors; Anticoagulants; Drug Therapy, Combination; Stroke; Fibrinolytic Agents; Myocardial Infarction; Hemorrhage; Myocardial Revascularization; Proportional Hazards Models; Propensity Score; Incidence; Republic of Korea
PubMed: 38915283
DOI: 10.3346/jkms.2024.39.e191 -
BMC Pulmonary Medicine Jun 2024The notion of a constant relationship between resistance and capacitance (RC time) in the pulmonary circulation has been challenged by more recent research. The RC time...
The notion of a constant relationship between resistance and capacitance (RC time) in the pulmonary circulation has been challenged by more recent research. The RC time can be obtained using either a simplified empirical approach or a semilogarithmic equation. Although direct curve-fit analysis is a feasible and ostensibly reference approach for RC analysis, it remains largely unexplored. We aimed to study the relationship between various RC methods in different states of pulmonary hemodynamics. Methods In total, 182 patients underwent clinically indicated right heart catheterization. The pressure curves were exported and processed using the MATLAB software. We calculated the RC time using the empirical method (RC), semilogarithmic approach (RC), and direct measurement of curve fit (RC). Results Among 182 patients, 137 had pulmonary hypertension due to left heart disease (PH-LHD), 35 had pulmonary arterial hypertension (PAH), and 10 demonstrated normal hemodynamics (non-PH). RC consistently overestimated the RC and RC measurements by a mean of 75%. With all three methods, the RC values were longer in the PAH (RC = 0.36 ± 0.14 s) than in the PH-LHD (0.27 ± 0.1 s) and non-PH (0.27 ± 0.09 s) groups (p < 0.001). Although the RC and RC values were similar among the three subgroups, they exhibited broad limits of agreement. Finally, the RC demonstrated a strong discriminatory ability (AUC = 0.86, p < 0.001, CI = 0.79-0.93) in identifying PAH. Conclusion RC time in PAH patients was substantially prolonged compared to that in PH-LHD and non-PH patients. The use of the empirical formula yielded systematic RC overestimation. In contrast, the semilogarithmic analysis provided reliable RC estimates, particularly for group comparisons.
Topics: Humans; Male; Female; Pulmonary Artery; Middle Aged; Cardiac Catheterization; Aged; Hypertension, Pulmonary; Vascular Resistance; Adult; Hemodynamics; Vascular Capacitance; Pulmonary Arterial Hypertension
PubMed: 38914995
DOI: 10.1186/s12890-024-03107-5 -
Pharmacological Reviews Jun 2024Voltage-gated sodium (Na) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to...
Voltage-gated sodium (Na) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to nervous system diseases such as epilepsy, neuropathic pain, psychosis, autism and cardiac arrhythmia. Many venom peptides selectively act on Na channels. These include conotoxins, which are neurotoxins secreted by cone snails for prey capture or self-defense, but which are also valuable pharmacological tools for the identification and/or treatment of human diseases. Typically, conotoxins contain two or three disulfide bonds and these internal cross-braces contribute to conotoxins having compact, well-defined structures and high stability. Of the conotoxins containing three disulfide bonds some selectively target mammalian Na channels and can block, stimulate, or modulate these channels. Such conotoxins have great potential to serve as pharmacological tools for studying the functions and characteristics of Na channels or as drug leads for neurological diseases related to Na channels. Accordingly, discovering or designing conotoxins targeting Na channels with high potency and selectivity is important. The amino acid sequences, disulfide bond connectivity, and three-dimensional structures are key factors that affect the biological activity of conotoxins, and targeted synthetic modifications of conotoxins can greatly improve their activity and selectivity. This review examines Na channel-targeted conotoxins, focusing on their structures, activities and designed modifications, with a view towards expanding their applications. Na channels are crucial in various neurological diseases. Some conotoxins selectively target Na channels, causing either blockade or activation, thus enabling their use as pharmacological tools for studying the channels' characteristics and functions. Conotoxins also have promising potential to be developed as drug leads. The disulfide bonds in these peptides are important for stabilizing their structures, thus leading to enhanced specificity and potency. Together, conotoxins targeting Na channels have both immediate research value and promising future application prospects.
PubMed: 38914468
DOI: 10.1124/pharmrev.123.000923 -
PloS One 2024Non-alcoholic fatty liver disease (NAFLD) is independently associated with atrial fibrillation (AF) risk. The uric acid (UA) to high-density lipoprotein cholesterol...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is independently associated with atrial fibrillation (AF) risk. The uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) has been shown to be closely associated with cardiovascular disease (CVD) and NAFLD. The aim of this study is to clarify whether elevated UHR is associated with the occurrence of AF in patients with NAFLD and to determine whether UHR predicted AF.
METHODS
Patients diagnosed with NAFLD in the Department of Cardiovascular Medicine of the Second Hospital of Shanxi Medical University from January 1, 2020, to December 31, 2021, were retrospectively enrolled in this study. The study subjects were categorized into AF group and non-AF group based on the presence or absence of combined AF. Logistic regression was performed to evaluate the correlation between UHR and AF. Sensitivity analysis and subgroup interaction analysis were performed to verify the robustness of the study results. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for UHR to predict the development of AF in patients with NAFLD.
RESULTS
A total of 421 patients with NAFLD were included, including 171 in the AF group and 250 in the non-AF group. In the univariate regression analysis, NAFLD patients with higher UHR were more likely to experience AF, and the risk of AF persisted after confounding factors were adjusted for (OR: 1.010, 95%CI: 1.007-1.013, P<0.001). AF risk increased with increasing UHR quartile (P for trend < 0.001). Despite normal serum UA and HDL-C, UHR was still connected with AF in patients with NAFLD. All subgroup variables did not interact significantly with UHR in the subgroup analysis. The ROC curve analysis showed that the areas under the curve for UA, HDL-C, and UHR were 0.702, 0.606, and 0.720, respectively, suggesting that UHR has a higher predictive value for AF occurrence in NAFLD patients compared to HDL-C or UA alone.
CONCLUSION
Increased UHR level was independently correlated with a high risk of AF in NAFLD patients.
Topics: Humans; Uric Acid; Atrial Fibrillation; Non-alcoholic Fatty Liver Disease; Male; Female; Cholesterol, HDL; Middle Aged; Retrospective Studies; ROC Curve; Risk Factors; Aged; Adult
PubMed: 38913677
DOI: 10.1371/journal.pone.0305952 -
JAMA Network Open Jun 2024Racial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with...
IMPORTANCE
Racial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with these disparities is unclear.
OBJECTIVE
To determine whether medical center racial and ethnic composition is associated with overall anticoagulation and disparities in anticoagulation for AF.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective cohort study of Black, White, and Hispanic patients with incident AF from 2018 to 2021 at 140 Veterans Health Administration medical centers (VAMCs). Data were analyzed from March to November 2023.
EXPOSURE
VAMC racial and ethnic composition, defined as the proportion of patients from minoritized racial and ethnic groups treated at a VAMC, categorized into quartiles. VAMCs in quartile 1 (Q1) had the lowest percentage of patients from minoritized groups (ie, the reference group).
MAIN OUTCOMES AND MEASURES
The odds of initiating any anticoagulant, direct-acting oral anticoagulant (DOAC), or warfarin therapy within 90 days of an index AF diagnosis, adjusting for sociodemographics, medical comorbidities, and facility factors.
RESULTS
The cohort comprised 89 791 patients with a mean (SD) age of 73.0 (10.1) years; 87 647 (97.6%) were male, 9063 (10.1%) were Black, 3355 (3.7%) were Hispanic, and 77 373 (86.2%) were White. Overall, 64 770 individuals (72.1%) initiated any anticoagulant, 60 362 (67.2%) initiated DOAC therapy, and 4408 (4.9%) initiated warfarin. Compared with White patients, Black and Hispanic patients had lower rates of any anticoagulant and DOAC therapy initiation but higher rates of warfarin initiation across all quartiles of VAMC racial and ethnic composition. Any anticoagulant therapy initiation was lower in Q4 than Q1 (69.8% vs 74.9%; adjusted odds ratio [aOR], 0.80; 95% CI, 0.69-0.92; P < .001). DOAC and warfarin initiation were also lower in Q4 than in Q1 (DOAC, 69.4% vs 65.3%; aOR, 0.85; 95% CI, 0.74-0.97; P < .001; warfarin, 5.4% vs 4.5%; aOR, 0.82; 95% CI, 0.67-1.00; P < .001). In adjusted models, patients in Q4 were significantly less likely to initiate any anticoagulant therapy than those in Q1 (aOR, 0.88; 95% CI, 0.78-0.99). Patients in Q3 (aOR, 0.75; 95% CI, 0.60-0.93) and Q4 (aOR, 0.69; 95% CI, 0.55-0.87) were significantly less likely to initiate warfarin therapy than those in Q1. There was no significant difference in the adjusted odds of initiating DOAC therapy across racial and ethnic composition quartiles. Although significant Black-White and Hispanic-White differences in initiation of any anticoagulant, DOAC, and warfarin therapy were observed, interactions between patient race and ethnicity and VAMC racial composition were not significant.
CONCLUSIONS AND RELEVANCE
In a national cohort of VA patients with AF, initiation of any anticoagulant and warfarin, but not DOAC therapy, was lower in VAMCs serving more minoritized patients.
Topics: Humans; Atrial Fibrillation; Male; Female; Aged; Anticoagulants; Retrospective Studies; United States; Healthcare Disparities; United States Department of Veterans Affairs; Middle Aged; Warfarin; Hispanic or Latino; Aged, 80 and over; Ethnicity; White People
PubMed: 38913375
DOI: 10.1001/jamanetworkopen.2024.18114 -
JACC. Case Reports Jul 2024A previously healthy man presented in shock due to incessant tachycardia. He ultimately required extracorporeal membrane oxygenation for support and clipping of his...
A previously healthy man presented in shock due to incessant tachycardia. He ultimately required extracorporeal membrane oxygenation for support and clipping of his appendage for arrhythmia control. This case highlights the importance of early recognition of cardiogenic shock, aggressive hemodynamic support, and a multidisciplinary approach to managing these challenging arrhythmias.
PubMed: 38912316
DOI: 10.1016/j.jaccas.2024.102375 -
European Heart Journal. Case Reports Jun 2024Previous literature suggests that patients with transthyretin amyloidosis (ATTR) experience a high burden of ventricular arrhythmias. Despite this evidence, optimal...
BACKGROUND
Previous literature suggests that patients with transthyretin amyloidosis (ATTR) experience a high burden of ventricular arrhythmias. Despite this evidence, optimal strategies for arrhythmia prevention and treatment remain subject to debate.
CASE SUMMARY
We report the case of a patient with hereditary ATTR cardiomyopathy who developed recurrent ventricular tachycardia prior to a decline in his left ventricular ejection fraction (LVEF). Although he ultimately received an intracardiac device (ICD) for secondary prevention of ventricular tachycardia, his clinical course begets the question of whether more aggressive arrhythmia prevention upfront could have prevented his global functional decline.
DISCUSSION
Given the advent of new disease-modifying therapies for ATTR, it is imperative to reconsider antiarrhythmic strategies in these patients. New decision tools are needed to decide what additional parameters (beyond LVEF ≤ 35%) may warrant ICD placement for primary prevention of ventricular arrhythmias in these patients.
PubMed: 38912115
DOI: 10.1093/ehjcr/ytae273