BACKGROUND: Rheumatic heart disease with persistent atrial fibrillation (RHD-AF) is associated with increased morbidity. However, there is no standardized approach for the maintenance of sinus rhythm (SR) in them. We aimed to determine the utility of a stepwise approach to achieve SR in RHD-AF.
METHODS: Consecutive patients with RHD-AF from July 2021 to August 2023 formed the study cohort. The stepwise approach included pharmacological rhythm control and/or electrical cardioversion (Central illustration). In patients with recurrence, additional options included AF ablation or pace and ablate strategy with conduction system pacing or biventricular pacing. Clinical improvement, NT-proBNP, 6-Minute Walk Test (6MWT), heart failure (HF) hospitalizations, and thromboembolic complications were documented during follow-up.
RESULTS: Eighty-three patients with RHD-AF (mean age 56.13 ± 9.51 years, women 72.28%) were included. Utilizing this approach, 43 (51.81%) achieved and maintained SR during the study period of 11.04 ± 7.14 months. These patients had improved functional class, lower NT-proBNP, better distance covered for 6MWT, and reduced HF hospitalizations. The duration of AF was shorter in patients who achieved SR, compared to those who remained in AF (3.15 ± 1.29 vs 6.93 ± 5.23, p = 0.041). Thirty-five percent (29) maintained SR after a single cardioversion over the study period. Only one underwent AF ablation. Of the 24 who underwent pace and ablate strategy, atrial lead was implanted in 22 (hybrid approach), and 50% of these achieved and maintained SR. Among these 24, none had HF hospitalizations, but patients who maintained SR had further improvement in clinical and functional parameters.
CONCLUSIONS: RHD-AF patients who could achieve SR with a stepwise approach, had better clinical outcomes and lower HF hospitalizations.

The objective of this network meta-analysis was to assess the efficacy and safety of apixaban, dabigatran, rivaroxaban, and edoxaban in patients diagnosed with atrial fibrillation and valvular heart disease. A comprehensive search was conducted across various electronic databases, including PubMed, Embase, and Web of Science, from inception to February 15, 2024. The search strategy utilized a combination of medical subject headings (MeSH) terms and relevant keywords related to valvular heart disease, atrial fibrillation, anticoagulant therapy, and study design, such as randomized controlled trials and observational studies. The outcomes evaluated in this analysis comprised the incidence of stroke or systemic embolism (SE), as well as the occurrences of major bleeding events. A total of 10 studies were incorporated into this meta-analysis, encompassing 40,662 participants. Of these, 12,385 received apixaban, 2,829 received dabigatran, 13,662 received rivaroxaban, 2,582 received edoxaban, and 9,202 received warfarin. The duration of follow-up in the included studies ranged from 3 to 54 months. Among the four direct oral anticoagulants (DOACs) studied, apixaban demonstrated a significant reduction in the risk of stroke or SE when compared to other DOACs and warfarin, highlighting its efficacy in patients with atrial fibrillation and valvular heart disease. Additionally, apixaban exhibited a lower risk of major bleeding events, further emphasizing its favorable safety profile compared to the other agents assessed. In conclusion, our findings suggest that apixaban may be more effective and safer than other DOACs and warfarin in this patient population. However, additional studies are warranted to compare the various DOACs in this cohort to identify the optimal treatment strategy for preventing adverse outcomes.

The prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) are well known indicators for adverse outcomes in various diseases, but there is no evidence on their association with the risk of left atrial thrombus (LAT) in patients with valvular atrial fibrillation (VAF).
A comparative cross-sectional analytical study was conducted on 433 VAF patients. Demographics, clinical characteristics and echocardiographic data were collected and analyzed. Patients were grouped by the presence of LAT detected by transesophageal echocardiography.
LAT were identified in 142 patients (32.79%). The restricted cubic splines showed an L-shaped relationship between PNI and LAT. The dose-response curve flattened out near the horizontal line with OR = 1 at the level of 49.63, indicating the risk of LAT did not decrease if PNI was greater than 49.63. GNRI was negative with the risk of LAT and tended to be protective when greater than 106.78. The best cut-off values of PNI and GNRI calculated by receiver operating characteristics curve to predict LAT were 46.4 (area under these curve [AUC]: 0.600, 95% confidence interval [CI]:0.541-0.658, P = 0.001) and 105.7 (AUC: 0.629, 95% CI:0.574-0.684, P<0.001), respectively. Multivariable logistic regression analysis showed that PNI ≤ 46.4 (odds ratio: 2.457, 95% CI:1.333-4.526, P = 0.004) and GNRI ≤ 105.7 (odds ratio: 2.113, 95% CI:1.076-4.149, P = 0.030) were independent predictors of LAT, respectively.
Lower nutritional indices (GNRI and PNI) were associated with increased risk for LAT in patients with VAF.

UNASSIGNED: Currently approved direct oral anticoagulants (DOACs) target thrombin or coagulation factor Xa. Administered in fixed doses without routine laboratory monitoring, DOACs have simplified the approach to oral anticoagulation, when previously the choice was limited to vitamin K antagonists (VKAs).
UNASSIGNED: We discuss a) unresolved issues related to optimal use of DOACs and b) new developments including the potential for FXIa inhibitors to be effective and safer anticoagulants.
UNASSIGNED: By simplifying oral anticoagulation, DOACs have facilitated the uptake of anticoagulation. The DOACs are approved for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism, and their indications are expanding to include the prevention of atherothrombosis. DOACs have now replaced vitamin K antagonists (VKAs) for most indications, but not all. DOACs are inferior to VKAs for patients with mechanical heart valves, left ventricular assist device, rheumatic atrial fibrillation, and those with antiphospholipid syndrome, and their safety and efficacy are uncertain in some populations (e.g. advanced renal and liver disease). Impediments to use include concerns for bleeding and cost. The newly developed FXIa and FXIIa inhibitors have the potential to be safer than current anticoagulants, but phase 3 trials are needed to confirm their clinical efficacy and safety.

OBJECTIVE: The efficacy of factor Xa inhibitors in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD) is unknown.
RESULTS: The objective of this article was to conduct a comprehensive evaluation of the INVICTUS trial, an open-label randomized controlled study that compared vitamin K antagonists (VKA) to rivaroxaban in patients with AF and RHD while also considering the existing evidence from literature in this particular area of research.
CONCLUSIONS: The findings of the INVICTUS trial indicated that rivaroxaban was found to be inferior in efficacy to VKA. However, it is important to note that the primary outcome of the trial was driven by sudden death and death caused by mechanical pump failure. As a result, it is necessary to approach the data from this study with caution, and it would be inappropriate to draw parallel conclusions for other causes of valvular AF. Particularly, the perplexing issue of how rivaroxaban could have contributed to both pump failure and sudden cardiac death requires further explanation. Additional data regarding changes in heart failure medication and ventricular function would be essential for proper interpretation.

Inflammation has been implicated in the progressive exacerbation of valvular atrial fibrillation (VAF) and thrombogenesis. This study aimed to analyze the association of systemic inflammation as measured by six indices with left atrial thrombus (LAT) in patients with VAF.
This comparative cross-sectional analytical study included 434 patients with VAF. Logistic regression analysis was used to assess the predictive value of LAT using six inflammation indices: neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio (MLR), white blood cell-to-mean platelet volume ratio, neutrophil-to-mean platelet volume ratio, systemic immune inflammation index, and systemic inflammation response index. Receiver operating characteristic curves were plotted, and the area under these curves (AUC) were calculated to evaluate the discriminative ability of the indices.
Transesophageal echocardiography revealed LAT in 143 (32.9%) patients. All six indices reflected a positive correlation with C-reactive protein levels. Multivariate logistic analysis revealed that these indices were independent predictors of LAT, and MLR appeared to perform best (odds ratio 12.006 [95% confidence interval (CI) 3.404-42.347]; P < 0.001; AUC 0.639 [95% CI 0.583-0.694]; P < 0.001).
Selected inflammatory indices were significantly and independently associated with LAT among patients with VAF.

UNASSIGNED: This study was performed to assess the effect of preablation glycemic control on atrial fibrillation recurrence rates after heart valve surgery concomitant with Cox-Maze IV ablation.
UNASSIGNED: Twelve-month preablation trends in glycemic control were studied. Recurrence and clinical outcome data were obtained during a mean follow-up period of 36.7 ± 23.3 months postablation.
UNASSIGNED: Higher glycated hemoglobin (HbA1c) at the time of ablation was associated with higher postablation recurrence rates. The cumulative atrial fibrillation recurrence-free survival of patients with HbA1c ≥7.5% at the time of operation at 12, 24, 36 and 48 months was 97.1, 78.3, 54.2, and 36.3%, respectively (P < 0.001), and 100, 84.9, 37.2, and 16.2% for patients who preoperatively had an upward trend in HbA1c, respectively (P < 0.001).
UNASSIGNED: Maintaining a downward trend in HbA1c during the 12-month period before the operation and an HbA1c value < 7.5% at the time of the operation reduced the recurrence of AF among patients who underwent heart valve surgery concomitant with the Cox-Maze IV procedure.

Background: The present study aimed to explore the correlation between calcium-activated potassium channels, left atrial flow field mechanics, valvular atrial fibrillation (VAF), and thrombosis. The process of transforming mechanical signals into biological signals has been revealed, which offers new insights into the study of VAF. Methods: Computational fluid dynamics simulations use numeric analysis and algorithms to compute flow parameters, including turbulent shear stress (TSS) and wall pressure in the left atrium (LA). Real-time PCR and western blotting were used to detect the mRNA and protein expression of IKCa2.3/3.1, ATK1, and P300 in the left atrial tissue of 90 patients. Results: In the valvular disease group, the TSS and wall ressure in the LA increased, the wall pressure increased in turn in all disease groups, mainly near the mitral valve and the posterior portion of the LA, the increase in TSS was the most significant in each group near the mitral valve, and the middle and lower part of the back of the LA and the mRNA expression and protein expression levels of IKCa2.3/3.1, AKT1, and P300 increased (p < 0.05) (n = 15). The present study was preliminarily conducted to elucidate whether there might be a certain correlation between IKCa2.3 and LA hemodynamic changes. Conclusions: The TSS and wall pressure changes in the LA are correlated with the upregulation of mRNA and protein expression of IKCa2.3/3.1, AKT1, and P300.

Atrial fibrillation (AF) is an abnormal heart rhythm related to an increased risk of heart failure, dementia, and stroke. The distinction between valvular and non-valvular AF remains a debate. In this study, proteomics and metabolomics were integrated to describe the dysregulated metabolites and proteins of AF patients relative to sinus rhythm (SR) patients. Totally 47 up-regulated and 41 down-regulated proteins in valvular AF, and 59 up-regulated and 149 down-regulated proteins in non-valvular AF were recognized in comparison to SR patients. Moreover, 58 up-regulated and 49 significantly down-regulated metabolites in valvular AF, and 47 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF patients were identified in comparison to SR patients. Based on analysis of differential levels of metabolites and proteins, 15 up-regulated and 22 down-regulated proteins, and 13 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF were identified relative to valvular AF. KEGG pathway enrichment analysis showed the altered proteins and metabolites were significantly related to multiple metabolic pathways, such as Glycolysis/Gluconeogenesis. Interestingly, the enrichment pathways related to non-valvular AF were obviously different from those in valvular AF. For example, valvular AF was significantly related to Glycolysis/Gluconeogenesis, but non-valvular AF was more related to Citrate cycle (TCA cycle). Correlation analysis between the differentially expressed proteins and metabolites was also performed. Several hub proteins with metabolites were identified in valvular AF and non-valvular AF. For example, Taurine, D-Threitol, L-Rhamnose, and DL-lactate played crucial roles in valvular AF, while Glycerol-3-phosphate dehydrogenase, Inorganic pyrophosphatase 2, Hydroxymethylglutaryl-CoAlyase, and Deoxyuridine 5-triphosphate nucleotidohydrolase were crucial in non-valvular AF. Then two hub networks were recognized as potential biomarkers, which can effectively distinguish valvular AF and non-valvular persistent AF from SR samples, with areas under curve of 0.75 and 0.707, respectively. Hence, these metabolites and proteins can be used as potential clinical molecular markers to discriminate two types of AF from SR samples. In summary, this study provides novel insights to understanding the mechanisms of AF progression and identifying novel biomarkers for prognosis of non-valvular AF and valvular AF by using metabolomics and proteomics analyses.

Background: Direct oral anticoagulants (DOACS) are approved for use in non-valvular atrial fibrillation (AF). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of DOACs vs. warfarin and update the evidence for treatment of AF and valvular heart disease (VHD). Methods: We identified randomized clinical trials (RCTs) and post-hoc analyses comparing the use of DOACS and Warfarin in AF and VHD, including biological and mechanical heart valves (MHV), updating from 2010 to 2020. Through systematic review and meta-analysis, by using the \"Rev Man\" program 5.3, the primary effectiveness endpoints were stroke and systemic embolism (SE). The primary safety outcome was major bleeding, while the secondary outcome included intracranial hemorrhage. We performed prespecified subgroup analyses. Data were analyzed by risk ratio (RR) and 95% confidence interval (CI) and the I-square (I 2) statistic as a quantitative measure of inconsistency. Risk of bias and methodological quality assessment of included trials was evaluated with the modified Cochrane risk-of-bias tool. Results: We screened 326 articles and included 8 RCTs (n = 14.902). DOACs significantly reduced the risk of stroke/SE (RR 0.80, 95% CI: 0.68-0.94; P = 0.008; moderate quality evidence; I 2 = 2%) and intracranial hemorrhage (RR 0.40, 95% CI: 0.24-0.66; P = 0.0004; I 2 = 49%) with a similar risk of major bleeding (RR 0.83, 95% CI: 0.56-1.24; P = 0.36; I 2 = 88%) compared to Warfarin. Conclusions: In this update, DOACs remained with similar efficacy and safety compared to warfarin in thromboprophylaxis for AF and VHD.