Metabolomics in atrial fibrillation - A review and meta-analysis of blood, tissue and animal models.
Journal of molecular and cellular cardiology
BACKGROUND:Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia associated with severe cardiovascular complications. AF presents a growing global challenge, however, current treatment strategies for AF do not address the underlying pathophysiology. To advance diagnosis and treatment of AF, a deeper understanding of AF root causes is needed. Metabolomics is a fast approach to identify, quantify and analyze metabolites in a given sample, such as human serum or atrial tissue. In the past two decades, metabolomics have enabled research on metabolite biomarkers to predict AF, metabolic features of AF, and testing metabolic mechanisms of AF in animal models. Due to the field's rapid evolution, the methods of AF metabolomics studies have not always been optimal. Metabolomics research has lacked standardization and requires expertise to face methodological challenges. PURPOSE OF THE REVIEW:We summarize and meta-analyze metabolomics research on AF in human plasma and serum, atrial tissue, and animal models. We present the current progress on metabolic biomarkers candidates, metabolic features of clinical AF, and the translation of metabolomics findings from animal to human. We additionally discuss strengths and weaknesses of the metabolomics method and highlight opportunities for future AF metabolomics research.
10.1016/j.yjmcc.2024.10.011
Neural repair function of osteopontin in stroke and stroke‑related diseases (Review).
Experimental and therapeutic medicine
Stroke, including hemorrhagic stroke and ischemic stroke, is a common disease of the central nervous system. It is characterized by a high mortality and disability rate and is closely associated with atherosclerosis, hypertension hyperglycemia, atrial fibrillation and unhealthy living habits. The continuous development of surgery and medications has decreased the mortality rate of patients with stroke and has greatly improved the disease prognosis. At present, the direction of clinical treatment and research has gradually shifted to the repair of nerve function after stroke. Osteopontin (OPN) is a widely distributed extracellular matrix protein. Due to its structural characteristics, OPN can be cut and modified into terminal fragments with different functions, which play different roles in various pathophysiological processes, such as formation of tumors, inflammation and autoimmune diseases. It has also become a potential diagnostic and therapeutic marker. In order to comprehensively analyze the specific role of OPN in nerve repair and its relationship with stroke and stroke-related diseases, the following key words were used: 'Osteopontin, stroke, atherosis, neuroplasticity, neural repair'. PubMed, Web of Science and Cochrane articles related to OPN were searched and summarized. The present review describes the OPN structure, isoforms, functions and its neural repair mechanism, and its association with the occurrence and development of stroke and related diseases was explored.
10.3892/etm.2024.12749
Physical Activity, Cardiorespiratory Fitness and Atherosclerotic Cardiovascular Disease: Part 1.
Pulse (Basel, Switzerland)
Background:The cardioprotective benefits and prognostic significance of regular moderate-to-vigorous physical activity (PA), increased cardiorespiratory fitness (CRF), or both are often underappreciated by the medical community and the patients they serve. Individuals with low CRF are two to three times more likely to die prematurely from atherosclerotic cardiovascular disease (CVD), than their fitter counterparts when matched for risk factor profile or coronary artery calcium (CAC) score. Accordingly, part 1 of this 2-part review examines these relations and the potential underlying mechanisms of benefit (e.g., exercise preconditioning) on atherosclerotic CVD, with specific reference to gait speed and mortality, CRF and PA as separate risk factors, and the relation between CRF and/or PA on attenuating the adverse impact of an elevated CAC score, as well as potentially favorably modifying CAC morphology, and on incident atrial fibrillation, all-cause and cardiovascular mortality, and on sudden cardiac death (SCD). Summary:We explore the underappreciated cardioprotective effects of regular PA and CRF. Part 1 examines how CRF and PA reduce the risk of premature death from atherosclerotic CVD by investigating their roles as separate risk factors, the potential underlying mechanisms of benefit, and their impact on gait speed, mortality, and atrial fibrillation. The review also addresses how CRF and PA may mitigate the adverse impact of an elevated CAC score, potentially modifying CAC morphology, and reduce the risk of SCD. Key Messages:Regular PA and high CRF are essential for reducing the risk of premature death from CVD and mitigating the negative impact of elevated CAC scores. Additionally, they provide significant protection against SCD and atrial fibrillation, emphasizing their broad cardioprotective effects.
10.1159/000541165
Can the Charlson comorbidity index help to guide DOAC dosing in patients with atrial fibrillation and improve the efficacy and safety of treatment? A subanalysis of the MAS study.
Current problems in cardiology
BACKGROUND:Frailty influences the effectiveness and safety of anticoagulant therapy in patients with atrial fibrillation (AF). The age-weighted Charlson comorbidity index may offer a valuable tool to assess the risk of adverse events in AF patients treated with direct oral anticoagulants (DOACs). This sub-analysis of MAS trial data aimed to assess whether using the Charlson index, instead of the standard criteria, would have led to different dosing and improved adverse event occurrence during treatment. METHODS:The MAS study looked for a relationship between DOAC levels assessed at baseline and adverse events during follow-up. The study is described in detail elsewhere. RESULTS:Among the 1,657 patients studied, 832 (50.2 %) had a relatively low Charlson index (up to 6, general median class), of whom 132 (15.9 %) were treated with reduced doses. Conversely, among the 825 patients with a high Charlson index (≥7), 257 (31.1 %) received standard doses. A weak but statistically significant positive correlation (r = 0.1413, p < 0.0001 by ANOVA) was observed between increasing Charlson classes and DOAC levels standardized to allow comparability among drug results. However, no significant differences were found in the incidence or number of adverse events during follow-up, or in other parameters, between patients with low and high Charlson's scores. CONCLUSIONS:Utilizing the Charlson index would have led to notable differences in DOAC dosing compared to standard criteria. However, we found no evidence that its use would have improved the prediction of adverse events in AF patients enrolled in the MAS study.
10.1016/j.cpcardiol.2024.102913
Atrial cardiomyopathy: An entity of emerging interest in the clinical setting.
European journal of internal medicine
Since 1995, the concept of atrial cardiomyopathy (ACM) has been associated with myocardial fibrosis. Despite a consensus document in 2016, ACM's definition primarily relies on histopathological findings. The focus on diagnostic criteria for ACM is driven by the potential link to thromboembolic events even independently on atrial fibrillation (AF). The complexity of the mutual relationships between ACM and AF makes difficult any assessment of the thromboembolic risk associated to ACM per se. ACM's thrombogenicity is a multifaceted clinical phenomenon involving electrical, functional, and structural modifications. Factors such as cardiovascular risk factors (e.g., hypertension), common cardiac comorbidities (e.g., heart failure), and extracardiac conditions (e.g., neuromuscular disorders) can promote atrial derangement, triggering atrial fibrillation (AF) and increasing the risk of thromboembolic events. Several diagnostic methods are available to detect the key features of ACM, including electrical changes assessed by surface and intracavitary ECG, and structural and functional alterations evaluated through echocardiography and cardiac magnetic resonance (CMR). These methods can be complemented by electro-anatomical mapping (EAM) to enhance the accuracy of myocardial tissue characterization and assessment of atrial fibrosis. Although certain clinical conditions (e.g., atrial high-rate episodes, AHREs; embolic stroke of undetermined source, ESUS) often exhibit atrial alterations in their thromboembolic presentations, recent randomized trials have failed to demonstrate the benefits of oral anticoagulation in patients with ACM without AF. However, ACM constitutes the substrate for the development of AF, as proposed in the AF European guidelines under the 4S-AF scheme. This review emphasizes the lack of a diagnostic gold standard and the need for clinical criteria for ACM, aiming to better understand the potential therapeutic implications of atrial structural and functional derangements, even in the absence of clinical evidence of AF.
10.1016/j.ejim.2023.10.023
Considerations regarding safety with pulsed field ablation for atrial fibrillation.
Heart rhythm O2
The introduction of pulsed field ablation (PFA) in electrophysiology marks a significant advancement, promising efficacy comparable to thermal ablation methods while potentially providing safety advantages. Despite a generally favorable safety profile in human trials and postmarket registries, cautious evaluation of PFA's safety is essential. This review provides a comprehensive overview of key safety considerations as we discuss a myriad of considerations ranging from thermal effects, gaseous microbubble formation, muscle contractions, and proarrhythmia to procedural techniques. We explore specific safety concerns with phrenic nerve injury, cerebral lesions, coronary artery spasm, hemolysis and pulmonary bleeding. Vigilance in safety monitoring, coupled with advancements in procedural techniques and understanding of PFA's unique effects, is crucial for optimizing the safe and effective use of PFA.
10.1016/j.hroo.2024.08.002
Comparative Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients with Chronic Liver Disease: A Systematic Review and Meta-analysis.
The Journal of innovations in cardiac rhythm management
Atrial fibrillation (AF) is a prevalent cardiac arrhythmia. Direct oral anticoagulants (DOACs), with superior efficacy and safety, have emerged as a promising alternative to warfarin. This systematic review and meta-analysis aimed to compare the safety and efficacy of DOACs and warfarin in patients with AF and chronic liver disease (CLD). A systematic search was undertaken in PubMed, the Cochrane Library, and Google Scholar to identify studies comparing the effectiveness of DOACs and warfarin in patients diagnosed with AF and CLD. Subsequent analyses were carried out using the random-effects model. This meta-analysis included eight studies involving 20,684 participants; baseline characteristics indicated a prevalent male presence (56.7%), with an average age of 61.63 ± 9 years. Primary outcomes demonstrated that DOACs were associated with significantly reduced all-cause mortality (relative risk [RR], 0.73; 95% confidence interval [CI], 0.56-0.95; = 84%; = .02) and ischemic stroke risk (RR, 0.62; 95% CI, 0.45-0.86; = 61%; = .004). Secondary outcomes revealed a significantly reduced risk of major bleeding with DOACs compared to warfarin, while gastrointestinal bleeding showed a non-significant decrease. Intracranial hemorrhage risk was significantly lower with DOACs compared to warfarin. DOACs demonstrate superior safety and efficacy compared to warfarin, evidenced by reduced rates of all-cause death, ischemic stroke, severe bleeding, and cerebral hemorrhage. Further randomized controlled trials are essential to enhance the evidence base for DOACs across diverse patient populations.
10.19102/icrm.2024.15103
Glucagon-like Peptide-1 Receptor Agonists in the Context of Pathophysiology of Diverse Heart Failure with Preserved Ejection Fraction Phenotypes: Potential Benefits and Mechanisms of Action.
Cardiac failure review
This review examines the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on different heart failure phenotypes with preserved ejection fraction (HFpEF). Traditional heart failure treatment modalities have shown limited success in improving outcomes for patients with HFpEF, but new evidence suggests that GLP-1RAs could be beneficial. The positive effects of GLP-1RAs are likely due to their ability to reduce systemic inflammation, enhance metabolism and directly affect the cardiovascular system, addressing critical aspects of HFpEF pathology. However, the exact impact of GLP-1RAs on clinical outcomes for different HFpEF phenotypes is still unclear. This review highlights both the potential benefits and the current limitations of GLP-1RA therapy, suggesting a careful approach for their application in clinical practice.
10.15420/cfr.2024.06