Absence Of Atrial Fibrillation Research Articles

Genetic Determinants of Left Atrial Function Are Associated With Stroke.

While atrial fibrillation (AF) is a key risk factor for stroke, recent studies have suggested that atrial cardiomyopathy may also increase stroke risk in the absence of AF. This study aimed to evaluate genetic determinants for left atrial (LA) function and volumes and risk of stroke. Polygenic scores (PGSs) for LA measures were constructed and used in 380 017 individuals in the UK Biobank, without history of ischemic stroke, systemic arterial embolism, or AF at enrollment. Risk of ischemic stroke was estimated using time-to-event models, considering all-cause death and incident AF as competing events. Systemic arterial embolism was investigated as a secondary end point. The PGS for LA passive emptying fraction was associated with risk of ischemic stroke. Individuals with a PGS for LA passive emptying fraction in the lowest quartile had a hazard ratio (HR) of 1.12 for ischemic stroke compared with those in the top quartile (P=0.004). These associations were robust in a subgroup free of prevalent cardiovascular disease at baseline (HR for lowest quartile versus top quartile, 1.22; P<0.001). No associations were found for 4 other PGSs for LA measures or for risk of systemic arterial embolism. Two-sample Mendelian randomization was conducted between LA measures and cardioembolic stroke and indicated a protective effect of higher LA functional measurements. The PGS for LA passive emptying fraction was significantly associated with incident ischemic stroke when considering AF as a competing risk. Consistent results were found in Mendelian randomization analyses. These findings suggest that atrial dysfunction may influence stroke risk independently of AF.

Abstract 4137695: Bundle Branch Block(BBB) is Independently Associated With Adverse Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejectionfraction(HFPEF): A Propensity Score Matched Analysis

Background: Ventricular dyssynchrony due to BBB can cause adverse cardiovascular(CV) outcomes in HF with reduced EF and is known to occur in HFpEF but its independent impact on is unclear. Objective: To determine if BBB is an independent risk factor for adverse HF outcomes in HFpEF and the impact of atrial fibrillation (AF).. Methods: We studied the impact of BBB in HFpEF utilizing propensity score(PS) matched cohorts without and with BBB from the TOPCAT Americas trial to account for confounding by other co-morbidities. Outcomes analyzed included the TOPCAT primary outcome, CV death&amp;hospitalization (CVH), sudden death, pump failure death (PFD), HF hospitalizations(H), and progression of HF. The impact of concomitant AF ( defined as any AF or AF on ECG) on these outcomes with and without BBB was analyzed. Results: 329 pts with HFpEF&amp;BBB were PS matched for 24 demographic&amp;disease state variables, BNP strata and AF status with a cohort of 329 pts with HFpEF without BBB. BBB was associated with increased risk of the TOPCAT primary outcome (Hazard ratio{HR} 1.44, 95% confidence intervals {CI} 1.10-1.89, p=0.008), increased risk of HF hospitalizations by 41%(HR 1.41 95% CI 1.04-1.91 p=0.0248) but not CVH (HR 1.18, 95% CI 0.93-1.49, p=..169), but not sudden death (HR 1.40, 95% CI 0.70-2.82, p=0.342) or CV death (HR 1.26, 95% CI 0.84-1.89, p=0.257). Risk of pump failure death (PFD) with BBB was significantly higher in HFpEF subjects without a history of AF (Figure left panel .Kaplan Meier Log rank p=0.0478, HR: 4.22, 95% CI: 0.89 to 19.87, p=0.0689) but not in AF (p=0.138). PFD risk was markedly higher in AF subjects without BBB ( Figure right, Kaplan Meier Log rank p=.0012, HR:7.99, 95% CI:1.80 to 35.41,p = 0.0063) than those with BBB (p=0.91) Conclusion: Ventricular dysynchrony induced by BBB independently worsens HFH risk in HFpEF. Its adverse impact on PFD iis seen in the absence of AF. Increase in PFD risk with AF in HFpEF subjects is most prominent in those with normal intraventricular conduction. Mechanical dyssynchrony induced by BBB may have a role in HFpEF subgroups with preserved atrioventricular filling, leading to these adverse HF outcomes

Investigating the role of an orphan nuclear receptor NR4A1 in atrial fibrillation

Abstract Introduction Atrial fibrosis is a major remodelling process in atrial fibrillation (AF). The lack of clinically effective drug targets, due to insufficient understanding of the mechanisms of cardiac fibrosis, hampers the treatment of AF. Orphan nuclear receptor subfamily 4 group A member 1 (NR4A1) is linked to fibrotic disease in multiple organs, however, its role in cardiac fibrosis and AF is yet to be demonstrated. Recent transcriptomic profiling revealed that NR4A1 expression is downregulated in human atrial cardiac fibroblasts (ACFs) in the presence of persistent AF. However, its mechanistic role in atrial fibrogenesis and AF is unknown. Purpose To investigate the expression profile and function of NR4A1 in human ACFs and provide insights into the role of NR4A1 in the context of persistent AF. Methods Human ACFs were isolated (enzymatic digestion) from right and left atrial appendages of 24 patients with persistent AF and controls in sinus rhythm (SR), who had elective heart surgery. NR4A1 knockdown in ACFs was achieved using NR4A1-siRNA. Gene and protein expression were determined by qPCR and western blot respectively, while BrdU assay and scratch assay were used to evaluate cell proliferation and migration. Atrial fibroblasts subpopulations were identified by single-nucleus RNA-sequencing. Subcellular localisation of NR4A1 was assessed by immunostaining, analysed by ImageJ. Results Validation of RNA-sequencing data confirmed a reduction of NR4A1 gene expression in human ACFs in persistent AF by 25% (p=0.029, Fig. 1A) and the NR4A1 predominant abundance in one of three identified subclusters of human ACFs (NR4A1+NAMPT+). The siRNA-mediated knockdown of NR4A1 in ACFs suppressed gene and protein expression of important component of extracellular matrix collagen-1 (Fig. 1B and Fig. 1C) and fibronectin protein (but not mRNA). The NR4A1-deficient cells also had decreased alpha-smooth muscle actin (αSMA) protein and gene expression (Fig. 1D and Fig. 1E), reduced periostin gene expression in the absence of changes in its protein. Furthermore, the NR4A1-deficiency reduced proliferation (by 18%, p=0.005, Fig. 1F) and accelerated migration (p=0.019, Fig. 1G) of human ACFs. These effects were independent of TGF-β1 stimulation, unlike reported in rat neonatal cardiac and dermal fibroblasts. Despite decreased NR4A1 gene expression, patients with AF had doubled NR4A1 protein levels compared to SR-ACFs (p=0.049, Fig. 2A). This was associated with abnormal 1.8-fold increase in the receptor subcellular localisation (p=0.032, Fig. 2B and Fig. 2C), as opposed to the physiological nuclear localisation observed in ACFs in the absence of AF. Conclusion While under physiological conditions, NR4A1 potently activates profibrotic processes in human ACFs, persistent AF patients have increased but abnormally distributed NR4A1 protein in atrial fibroblasts, whose consequences are yet to be determined in order to develop new therapies for AF.Figure 1Figure 2

Temporal trends in clinical outcomes in heart failure patients with and without atrial fibrillation: a nationwide study from 1997-2018

Abstract Background Given the many advances in treating heart failure (HF) and atrial fibrillation (AF) separately over the past decades, it remains unclear how the prognosis of patients diagnosed with both conditions has changed over time. Purpose We aimed to investigate the temporal trends in all-cause mortality, HF hospitalisation, and stroke from 1997 to 2018 in patients diagnosed with both HF and AF. Methods From Danish nationwide registries, we identified 152,059 patients with a first-time HF-diagnosis from 1997 to 2018. Patients were categorised into groups based on their AF status: prevalent AF (n=34,734), new-onset AF (n=12,691), and absence of AF (n=104,634). Patients were further subdivided into four year groups (1997-2001, 2002-2006, 2007-2012, 2013-2018), based on the year of HF onset. The primary outcome of interest was the absolute five-year risk of all-cause mortality, and key secondary outcomes were HF hospitalisation and stroke, investigated using the Aalen-Johansen estimator, accounting for competing risk of death. Results Between 1997 and 2018 the proportion of patients with new-onset HF and prevalent AF increased from 17.0% (n = 6,372) to 27.7% (n = 11,569), while those with concurrent new-onset AF increased from 7.7% (n = 2,884) to 8.1% (n = 3401). Contrary, the proportion of patients decreased among those with no AF from 75.3% (n = 28,235) to 64.2% (n = 26,850). The five-year risk of all-cause mortality decreased from 69.1% (95% CI): 67.9%-70.2%) to 51.3% (49.9%-52.7%), 62.3% (60.5%-64.4%) to 43.0% (40.5%-45.5%), and 61.9% (61.3%-62.4%) to 36.7% (35.9%-37.6%) for the prevalent AF, new-onset AF, and no AF group, respectively (Figure 1). The five-year risk of HF hospitalisation went from 33.3% (32.1%-34.4%) to 30.3% (29.2%-31.4%) in the prevalent AF group, from 25.8% (24.2%-27.4%) to 29.6% (27.7%-31.5%) in the new-onset AF group, and from 28.4% (27.8%-28.9%) to 28.0% (27.2%-28.6%) in the no AF group. The five-year risk of stroke decreased from 8.5% (7.8%-9.1%) to 5.0% (4.4%-5.5%) in the prevalent AF group, 8.2% (7.2%-9.2%) to 4.6% (3.7%-5.5%) in the new-onset AF group, and 6.3% (6.1%-6.6%) to 4.9% (4.6%-5.3%) in the no AF group (Figure 2). Simultaneously, the proportion of patients prescribed anticoagulant therapy within 90 days after HF onset increased from 42.7% to 93.1% in patients with prevalent AF and 41.9% to 92.5% in patients with new-onset AF. Conclusion From 1997 to 2018, we observed an increase in patients with HF and coexisting AF. The five-year risk of mortality and stroke decreased across all patient groups regardless of AF-status. Additionally, prescriptions of anticoagulation therapy increased, and stroke risk in patients with HF and AF was reduced to similar levels as patients with HF without AF at the end of the study period.Figure 1 - Mortality in HF patientsFigure 2 - Stroke risk in HF patients

Left atrial strain parameters are able to predict presence of atrial fibrillation

Abstract Background Three-dimensional speckle-tracking echocardiography allows evaluation of left atrial function, left atrial function has been assessed in various diseases for prognostication [1]. Atrial fibrillation (AF) is most common arrhythmia, and one of its manifestations is increased left atrial filling pressure and left atrial dilatation. Methods Echocardiography loops were collected between December 2019 and December 2021, only valid atrial loops, and sinus rhythm during examination. Spearman test was used for correlation matrices of left atrial parameters; uni- , multivariate and binary logistic regression to predict presence or absence of atrial fibrillation. Results A total of 116 patients (50% females) aged 76.9±11.2 were included in the analysis. Males and females differed in anthropometric and other clinical parameters. Intra- and interobserver variability was close to 1% since most of the measurements are semi-automatized. 2D and 3D left atrial volumes correlated significantly (r=0.8, P&amp;lt;0.0001, Fig.1). Almost all left atrial strain measurement uni- and multivariately predicted the presence of atrial fibrillation, binary logistic regression identified two most significant parameters (left atrial longitudinal strain reservoir and conduit phase, LASr, LAScd, P=0.042, P=0.044, respectively, Fig.2). LASr is significantly greater in patients without history of AF vs patient with AF history, (16±16, 10.5±7.1, respectively, P=0.012). The probability of sinus rhythm increases linearly with the increasing value of LASr. Conclusion Left atrial longitudinal strain was able to differentiate patients with paroxysmal atrial fibrillation as compared to patients without history of this arrhythmia.

Cardiovascular prevention with GLP1 agonists in high or very-high cardiovascular risk irrespective of diabetes

Abstract Introduction Patients with established cardiovascular disease have an increased risk of stroke and myocardial infarction, even in the absence of atrial fibrillation. Several trials have analyzed the effect of glucagon-like peptide-1 receptor (GLP1) agonists in patients with high cardiovascular risk and lately this effect has been studied even in the absence of diabetes. Methods A meta-analysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The primary objective of the study was to analyze the composite endpoint of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (MACE). As secondary objectives, cardiovascular death, non-fatal myocardial infarction and non-fatal stroke have been studied separately. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant. In the case of significant heterogeneity in the primary objective, a stratified analysis with exposure time have been performed to explain this outcome. Results A sum of 9 randomized controlled trials were included where a GLP1 agonist such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide was compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonist. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes and 60552 (77.9%) from cardiovascular disease. As showed in figure 1, the GLP1 agonists showed a reduction of 13% of the MACE (RR: 0.87, 95% CI 0.81-0.92; p&amp;lt;0.001). Heterogeneity could be explained by exposure time and concentration in the blood, considering that it disappears within each group when applying this condition. Treatment with GLP1 agonist also reduced cardiovascular death by 12% (RR: 0.88, 95% CI 0.82-0.94; p&amp;lt;0.001), non-fatal strokes by 14% (RR: 0.86, 95%CI 0.79-0.95; p&amp;lt;0.001) and non-fatal miocardial infarction by 13% (RR: 0.87, 95% CI 0.78-0.97; p&amp;lt;0.001). Conclusion Treatment with a GLP1 agonist reduced the incidence of the MACE by 13% and cardiovascular death by 12%, as well as it decreased the incidence of nonfatal stroke by 14% and of nonfatal myocardial infarction by 13% in different RCTs involving patients with high or very-high cardiovascular risk with or without diabetes.

Echocardiographic signs of atrial cardiopathy and MRI-detected silent brain infarcts in a middle-aged cohort: the Akershus Cardiac Examination 1950 Study

Abstract Background Atrial fibrillation (AF) is linked to clinical stroke and silent brain infarction (SBI). In the majority of AF patients, there exists a recognized form of atrial cardiopathy, and it is suggested that atrial cardiopathy, even in the absence of AF, may serve as a risk factor for stroke. However, existing evidence is limited, and it remains unclear whether atrial cardiopathy indeed poses a risk for stroke and SBI. Purpose We aimed to investigate the association between echocardiographic signs of atrial cardiopathy and the detection of SBI through magnetic resonance imaging (MRI) in a middle-aged cohort from the general population. Methods In the prospective Akershus Cardiac Examination (ACE) 1950 Study conducted within the general population in Norway, cardiovascular risk assessment including transthoracic echocardiography, was undertaken at study inclusion between 2012 and 2015. We assessed body surface area-indexed left atrial (LA) maximum and minimum volume, as well as LA reservoir and contractile strain. Subsequently, brain MRI was conducted in a subset of the cohort between 2017 and 2023. SBI was defined as presence of neuroimaging sign of infarcts, including lacunes, in individuals without a history of stroke. Logistic regression analyses were performed to explore the associations between echocardiographic measures of atrial cardiopathy and SBI on MRI, adjusting for sex, age, hypertension, and diabetes. Results A total of 397 out of 3706 (10.7%) participants in the ACE 1950 study underwent MRI examination and were included in this analysis. At the time of MRI, the mean age was 70.0±2.2 years, with 157 (40%) women, 248 (62%) with hypertension, and 36 (9%) with diabetes at study inclusion. SBI was present in 51 (13%), of which only 1 (2%) had known AF. After excluding 18 participants with pre-existing AF, no significant difference were observed in LA volumes or LA strain between participants with or without SBI (Figure 1). In unadjusted and adjusted logistic regression analyses, neither LA volume nor LA strain were associated with SBI (Table 1). Conclusion Echocardiographic signs of atrial cardiopathy were not associated with silent brain infarcts in a middle-aged cohort from the general population.

Objective functional improvement and vital prognosis after TAVR in patients with low-gradient aortic stenosis. Development of a predictive score

Abstract Introduction Patients with low-gradient aortic stenosis (mean gradient &amp;lt; 40 mmHg) (LGAS) supose a clinical challenge because in these patients the degree of functional recovery after TAVR could be lower and their prognostic evolution more adverse. This is relevant for the optimal indication of TAVR, especially with the growing number of patients with a borderline indication due to comorbidities or advanced age with certain degree of frailty. Purpose To develop a clinical model to predict the response to TAVR in LGAS patients based in non invasive physiological parameters at baseline. Methods In a cohort of patients undergoing TAVR a prospective evaluation of multiple pathophysiological parameters was performed derived from pre- and post-TAVR assessment with echocardiography, computed tomography, and non-invasive arterial pulse wave analysis with the Sphygmocor XCEL system. Objective functional improvement 6 months after TAVR was assessed by the 6-minute walk test and NT-proBNP levels. Clinical follow-up was performed at 1 year. Results Of the 450 patients included, 310 showed high aortic gradient and 140 (31%) low gradient, with an objective functional improvement in 90% and 64% (p&amp;lt;0.001) respectively, and with 1-year mortality of 4% and 12% (p=0.001). In the LGAS group, 1-year mortality was 20% in the subgroup without functional improvement and 8% (p=0.001) in the subgroup showing functional improvement. In the LGAS group, the pathophysiological parameters predictive of functional improvement were the augmentation index75 ≥ 45% (OR 4, CI 95% 1.9–11.3; p=0.006), posterior wall thickness ≤ 12 mm (OR 3.2, CI 95% 1.4–8; p=0.01) and absence of atrial fibrillation (OR 2.7, CI 95% 1.5–8.4; p=0.01). To generate a simple integer-based point score for each predictive variable, each beta coefficient was divided by the absolute value of the smallest coefficient, multiplied by 5, and rounded to the nearest integer. The values were 7, 6 and 5 respectively. Among the low-gradient population, in 55 patients with 0-6 score points the functional improvement was only 29%, while in the remaining 85 patients with 7-18 score points the functional improvement was 86% (p&amp;lt;0.001). Conclusions LGAS patients account for a relatively high proportion of patients undergoing TAVR. They show less objective functional recovery, which is associated with a significantly higher mortality at follow-up. We have developed a score based on 3 variables (augmentation index75, posterior wall thickness and atrial fibrillation) that can help predict the functional and prognostic response to TAVR in these patients.

Atrial Fibrillation Surgery in Australia: Are We Doing Enough?

This study aimed to examine contemporary burden and treatment trends of atrial fibrillation (AF) in patients undergoing cardiac surgery in Australia and New Zealand. This allows comparison of contemporary practice with the Society of Thoracic Surgeons guideline recommendations for the surgical treatment of AF in patients undergoing cardiac surgery. A 10-year retrospective review of the Australian & New Zealand Society of Cardiac & Thoracic Surgeons National Cardiac Surgery Database was performed, examining all adult cardiac surgery patients from 2011 to 2021. Patients were grouped by the presence or absence of AF, and simple descriptive statistical analysis was performed to assess baseline demographics and premorbid condition of the patients. The incidence of AF was analysed by type of surgery. Trends for surgical treatment of AF were then analysed using simple descriptive statistics, examining isolated left atrial appendage ligation, isolated surgical ablation, and combined ligation and ablation. In the last 10 years, the Australian & New Zealand Society of Cardiac & Thoracic Surgeons database has recorded 140,680 patients who underwent cardiac surgery. Atrial fibrillation (AF) was present in 21,077 patients (14%). Patients with AF were generally older (72.25 vs 66.65 years; p<0.001). Among patients undergoing cardiac surgery, AF was more common in female than in male patients (18% vs 13%, respectively). Patients with AF more often had a higher classification of dyspnoea according to the New York Heart Association and lower ejection fractions compared with their AF-free counterparts. The incidence of AF as a comorbid condition was more frequent in patients undergoing mitral valve surgery or combined coronary artery bypass grafting and valve surgery (aortic, mitral, or both) compared with those undergoing isolated coronary or aortic surgery. Only 11.90% (n=2,509) of patients with AF received a combined ablation and left atrial appendage ligation, and 19.54% (n=693) of those received a Cox-Maze IV ablation. The burden of concomitant AF in patients undergoing cardiac surgery in Australia is higher than previously reported (14% vs 5%-11%). Despite strong recommendation for the surgical management of AF in patients undergoing cardiac surgery and clear evidence of its benefit, both left atrial appendage ligation and surgical ablation independently or concomitantly remain heavily underutilised in this cohort.

Predicting Recanalization Failure With Conventional Devices During Endovascular Treatment Related to Vessel Occlusion

Background Among patients with stroke eligible for endovascular treatment, preprocedure identification of those with low chances of successful recanalization with conventional devices (stent‐retrievers and/or direct aspiration) may allow anticipating procedural rescue strategies. We aimed to develop a preprocedural algorithm able to predict recanalization failure with conventional devices (RFCD). Methods Observational study. Data from consecutive patients with stroke who received endovascular treatment between 2019 and 2022 in 10 centers were collected from the Catalan Stroke Registry (Codi Ictus Catalunya Registry, CICAT). RFCD was defined as final thrombolysis in cerebral infarction ≤2a or the use of rescue therapy defined as balloon angioplasty±stent deployment. Univariate and multivariate analysis to identify variables associated with RFCD were performed. A gradient boosted decision tree machine learning model to predict RFCD was developed utilizing preprocedure variables previously selected. Clinical improvement at 24 hours was defined as a drop of ≥4 points from baseline National Institutes of Health Stroke Scale score or 0–1 at 24 hours. Results In total, 984 patients were included; RFCD was observed in 14.3% (n:141) of the cases. Of these, 47.5% (n = 67) received balloon angioplasty±stent deployment as rescue therapy. Among patients receiving balloon angioplasty±stent deployment, clinical improvement was associated with lower number of attempts with conventional devices (median number of passes 2 versus 3; P = 0.045). In logistic regression, the absence of atrial fibrillation (odds ratio [OR]: 2.730, 95%CI: 1.541–4.836; P = 0.007) and no‐thrombolytic treatment (OR: 1.826, 95%CI: 1.230–2.711; P = 0.003) emerged as independent predictors of RFCD. A predictive model for RFCD, based on age, sex, hypertension, wake‐up stroke, baseline National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT [Computed Tomography] Score, occlusion site, thrombolysis, and atrial fibrillation showed an acceptable discrimination (area under the curve: 0.72±0.024 SD) and accuracy (0.75±0.015 SD). Overall performance was moderate (weighted F1‐score: 0.77±0.041 SD). Conclusion In RFCD patients, early balloon angioplasty±stent deployment rescue was associated with improved outcomes. A predictive model using affordable preprocedure clinical variables could be useful to identify these patients before intervention.

Right Atrial Thrombus Masquerading as Myxoma.

In-situ right atrial (RA) thrombus is a rare occurrence typically associated with heightened inflammatory or hypercoagulable states. Here, we present a case of in-situ RA thrombus mimicking atrial myxoma in a patient with sepsis and bacteraemia. A 41-year-old man presented with septic arthritis and bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA). A transoesophageal echocardiogram revealed a large pediculated mass resembling atrial myxoma, which was not visible on transthoracic echocardiography performed four days earlier. Cardiac magnetic resonance (CMR) imaging strongly suggested a thrombus, leading to the patient undergoing transcatheter aspiration. Subsequent pathology confirmed an organised fibrin thrombus without evidence of infection. The patient's in-situ RA thrombus likely developed in response to a heightened inflammatory state associated with sepsis. Limited data exist on in-situ RA thrombi in the absence of atrial fibrillation, though some reports suggest a correlation between heightened inflammation and a hypercoagulable state. CMR imaging is invaluable for characterising such masses and can aid in distinguishing a thrombus from a myxoma. Differentiating right atrial (RA) thrombus from myxoma: cardiac magnetic resonance imaging is essential for distinguishing RA thrombus from myxoma, preventing unnecessary surgeries.Hypercoagulable and inflammatory states: spontaneous in-situ RA thrombi can occur without deep vein thrombosis (DVT) or atrial fibrillation, especially in hypercoagulable and inflammatory conditions.Transcatheter aspiration: this less invasive alternative to surgery is effective for large, mobile RA thrombi, reducing embolisation risk.

The Role of 24-Hour Holter Electrocardiogram in the Early Detection of Atrial Fibrillation in Newly Diagnosed Acute Ischemic Stroke Patients.

Introduction Stroke is a leading cause of death and disability globally, with atrial fibrillation (AF) recognized as a significant risk factor due to its association with increased stroke recurrence and mortality. Timely detection of AF is crucial to prevent recurrent strokes and improve outcomes. This study primarily aimed to evaluate the utility of 24-hour Holter monitoring for AF detection in acute ischemic stroke patients. Methods This retrospective observational study examined data from 207 patients admitted with acute ischemic stroke to a tertiary-care hospital over a two-year period. Patients with pre-existing AF, transient ischemic attacks, unconfirmed diagnoses, and missing Holter reports were excluded. A total of 140 patients were included in the analysis. The study investigated AF detection rates, the relationship between AF and stroke risk factors, other Holter findings, and the time delay in attaching Holter monitors. Results Of the 140 patients evaluated, AF was detected in nine (6.4%), exclusively in those aged ≥65 years. The most prevalent risk factors among the study participants were hypertension (74.3%) and diabetes (61.4%). No significant correlations were observed between AF and the analyzed stroke risk factors. The median delay for Holter device attachment was 3,503 minutes (approximately two days and 10 hours), with longer delays noted in males (4,084 mins (approximately two days and 20 hours) vs. 2,565 mins (approximately one day and 18 hours), p=0.005). Premature atrial complexes(PACs) were notably associated with the absence of AF, suggesting their potential role as markers for undiagnosed AF. Conclusion The study highlights the limited utility of 24-hour Holter monitoring in detecting AF in acute ischemic stroke patients, advocating for extended monitoring durations, especially in older patients. To improve AF detection, potential strategies include using longer monitoring periods and optimizing hospital workflows to reduce delays in attaching Holter devices. These approaches can minimize the risk of underdiagnosing paroxysmal AF, thereby preventing recurrent strokes and improving patient outcomes. Further investigation into PACs as potential predictive markers for AF is warranted.

Autoimmune Disorders in Heart Failure With Preserved Ejection Fraction

BackgroundInflammation plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of an underlying systemic inflammatory disease such as rheumatoid arthritis or systemic lupus erythematosus. ObjectivesThis study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and autoimmune or primary inflammatory disorders. MethodsOf 982 consecutively evaluated patients with HFpEF diagnosed, 79 (8.0%) had autoimmune disorders. HFpEF was defined by invasive cardiopulmonary hemodynamic exercise testing. ResultsFemale sex, higher heart rate, lower hemoglobin, absence of atrial fibrillation, and absence of coronary artery disease were independently associated with autoimmune disorders. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with autoimmune disorders, reflected by lower arterial-venous oxygen content difference at rest (4.2 ± 0.7 mL/dL vs 4.6 ± 1.0 mL/dL; P < 0.001) and during exercise (9.3 ± 2.2 mL/dL vs 10.4 ± 2.2 mL/dL; P < 0.001), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCo2 slope, regression slope relating minute ventilation to carbon dioxide output) was also more impaired (38.0 ± 7.9 vs 36.2 ± 7.3; P = 0.043). Patients with autoimmune disorders had a higher risk of death or heart failure (HF) hospitalization compared with those without in adjusted analyses (HR: 1.95 [95% CI: 1.17-3.27]; P = 0.011) over a median follow-up of 3.0 years, which was primarily attributable to higher risk of HF hospitalization (HR: 2.87 [95% CI: 1.09-7.57]; P = 0.033). ConclusionsPatients with HFpEF and autoimmune disorders have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared with those without.

Predicting atrial fibrillation risk following embolic stroke of unknown source using cardiac magnetic resonance imaging

Abstract Background Approximately 25% of embolic strokes of unknown source (ESUS) are attributed to undiagnosed atrial fibrillation (AF).1 The European Stroke Organisation (ESO) recommends implantable loop recorder (ILR) monitoring to identify ESUS patients with AF, permit the initiation of anticoagulation and reduce risk of recurrent stroke.2 However, this approach delays treatment and carries significant cost and resource implications. An alternative approach, where early anticoagulation is initiated in the absence of AF has failed to reduce recurrent stroke in four randomised controlled trials (NAVIGATE ESUS, RE-SPECT ESUS, ATTICUS and ARCADIA).3-6 An urgent need exists for new strategies to identify ESUS patients with undiagnosed AF that are at high risk of future thromboembolism. Purpose The primary objective of this study was to produce a substrate-based predictive model for AF in ESUS patients using atrial cardiac magnetic resonance imaging (CMRi). Method The Atrial CARdiac Magnetic resonance imaging in patients with embolic stroke of unknown source without documented AF (CARM-AF) Study is a prospective, multi-centre, observational study. All patients underwent CMRi and ILR insertion for AF detection within 3 months of ESUS. The main inclusion criteria were expected survival &amp;gt;12 months, CHA2DS2VASc≥3 and eGFR &amp;gt;30ml/min. Patients were allocated to the study group if AF &amp;gt;30 seconds was detected by ILR during the first year of follow-up and control group if no AF detected (Figure 1). Univariable analysis was used to identify clinical, echocardiographic and CMR parameters associated with AF diagnosis. Parameters with p&amp;lt;0.2 and no co-linearity were used to develop multivariable logistic regression models for AF prediction. Results From September 2020 to September 2022, 102 patients were enrolled and 91 were included in the final analysis. AF was detected in 17 patients during the first year of follow-up (18.6%). In univariable analysis, patients with AF were more likely to be female (p=0.02), but there were no significant differences in age, race, body mass index (BMI) or CHA2DS2VASc score (p=0.06, 0.272, 0.195, 0.211) between groups. Increased left atrial (LA) volume, surface area and reduced LA ejection fraction were associated with increased risk of AF detection at 1 year (p=0.006, 0.044, 0.008). LA fibrosis and sphericity were not associated with AF (p=0.84, 0.98). Logistic regression models for AF risk prediction were developed using patient, echocardiographic and CMR parameters. A combined model of patient and CMR parameters outperformed assessment of patient characteristics alone, achieving an AUC of 0.85 for predicting AF occurrence (p&amp;lt;0.005). Pseudo R2 of 0.30 (McFadden) indicated excellent model fit (Figure 2). Conclusion CARM-AF is the first study to demonstrate feasibility and utility of CMR imaging to predict AF risk following ESUS. A randomised controlled trial initiating anticoagulation using the developed model is recommended.Study DesignModel Comparison (ROC Curves)

Development and validation of a SCORing systEm for pre-thrombectomy diagnosis of IntraCranial Atherosclerotic Disease (Score-ICAD)

BackgroundEarly identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of...

A COMPLEX CASE OF EARLY ONSET ATRIAL FIBRILLATION IN AN ENDURANCE ATHLETE: THE IMPORTANCE OF FAMILY HISTORY

Abstract Introduction Early onset atrial fibrillation (AF) in an endurance athlete represents a challenge for the cardiologist, especially in apparent absence of an overt structural heart disease. Different genetic variants have been associated with early onset AF but indications to genetic testing are still under definition. Case A 54–year–old man (BMI 19 kg/sqm), previous competitive athlete (Nordic running and walking) presented to the Emergency Department with sudden onset palpitations and dyspnea due to high penetrance AF (145 bpm). Family history (FH) was positive for cerebrovascular accidents in both parents and for early onset (&amp;lt;60 years) AF in the father. The man had a recent history of borderline hypertension, of effort related syncope of and of infundibular, isolated, premature ventricular complexes during a maximal exercise stress test (otherwise negative for ischemia) which ultimately led to the denial of competitive sport eligibility. Sinus rhythm (SR) was acutely restored with flecainide and the patient was discharged with low dose nadolol. Cardiac US showed normal left ventricular (LV) dimensions and thicknesses (10 mm), with regular LVEF (60%) and global longitudinal strain (–18%), mildly dilated left atrium (LAVI 36 ml/sqm) and bi–leaflet mitral valve prolapse without significant mitral regurgitation, mitro–anular disjunction nor Pickelhaube sign; 24h Holter ECG showed SR with rare supraventricular (SV) ectopic beats and a 4 beats SV run. Due to the recurrence of short episodes of palpitations, rhythm control with flecainide and antithrombotic prophylaxis were started and AF ablation was planned. Genetic testing for early onset AF identified a nonsense variant (c.84665delG; p.Gly28222fs*2) in TTN gene, classified as likely pathogenic (C4), so far not reported in scientific literature. Also, despite a moderate–low cardiovascular risk as assessed by SCORE2, mostly due to the FH and the desire to engage in high intensity exercise, coronary CT was prescribed, which showed a critical coronary disease leading to stenting on left anterior descending artery and intermediate branch. Cardiac MRI was planned. Conclusions Early onset AF in endurance athletes should not be underrated and a thorough examination including a detailed family history should be performed. TTN is the single gene most frequently associated with early onset AF in absence of an overt structural heart disease, but the subsequent clinical evolution is still largely unknown.

Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction

BackgroundRenin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear. MethodsWe analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30–60 mL/min/1.73 m2). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30–44, 45–59 mL/min/1.73 m2), systolic blood pressure (<120, ≥120 mmHg), LVEF (41–49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use. ResultsAmong patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74–86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43–0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups. ConclusionsApproximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes.

Arrhythmias and amyloidosis

Cardiac amyloidosis is an infiltrative cardiomyopathy characterized by the extracellular deposition of amyloid fibrils within the myocardium. Beyond heart failure, patients with cardiac amyloidosis commonly present with arrhythmias and conduction system disorders. Atrial fibrillation is observed in up to 80% of patients at the time of diagnosis, with patients typically maintaining normal heart rates due to concurrent atrioventricular nodal disease. The thromboembolic risk is particularly high in patients with cardiac amyloidosis, and left atrial thrombi have been observed even in the absence of atrial fibrillation. Conduction system diseases are also highly prevalent, often necessitating permanent pacemaker implantation. The use of implantable defibrillators in this population remains controversial. This overview of published data and therapeutic strategies related to arrhythmias and conduction system disorders aims to assist readers in decision-making in complex clinical scenarios.

Complex left appendage morphology is associated with Embolic Stroke of Undetermined Source.

Variations in the left atrial appendage (LAA) morphology are associated with different embolic risk in patients with atrial fibrillation (AF). Data are scarce regarding the association between LAA morphology and Embolic stroke of undetermined source (ESUS). Using cardiac computed tomography (CCT) scans, LAA morphology was categorized as either chicken wing (CW), cactus, windsock, or cauliflower. Furthermore, we examined the presence of large secondary lobes arising from the main lobe, considering their existence as indicative of a complex LAA morphology. LAA morphologies were compared between ESUS (n = 134) and AF patients (n = 120); and between ESUS patients with (n = 24) and without (n = 110) subsequent AF diagnosis during long-term follow-up. ESUS patients had a significantly higher prevalence of cauliflower morphology compared to AF group (52% vs 34%, respectively, p = 0.01); however, no significant difference was found between the groups when categorizing LAA morphology to either CW or non-CW. ESUS patients had significantly higher prevalence of large secondary lobes compared with AF patients (50% vs 29%, respectively, p = 0.001). When comparing ESUS patients with and without AF diagnosis during follow-up (20-48 months of follow-up, median 31 months), there were no significant differences in the prevalence of the "classical" morphologies, but large secondary lobes were significantly more prevalent among those without subsequent AF diagnosis. ESUS patients have a high prevalence of complex LAA morphology, which might be associated with an increased risk for thrombus formation even in the absence of AF.

Predictive nomogram models for atrial fibrillation in COPD patients: A comprehensive analysis of risk factors and prognosis.

The aim of the present study was to identify the independent risk factors and prognostic indicators for atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD) and to develop predictive nomogram models. This retrospective study included a total of 286 patients with COPD who were admitted to the Second Affiliated Hospital of Guilin Medical College between January 2020 and May 2022. The average age of the patients was 77.11±8.67 years. Based on the presence or absence of AF, the patients were divided into two groups: The AF group (n=87) and the non-AF group (n=199). Logistic regression analysis was conducted to identify variables with significant differences between the two groups. Nomogram models were constructed to predict the occurrence of AF in COPD patients and to assess prognosis. Survival analysis was performed using the Kaplan-Meier method. The follow-up period for the present study extended until April 31, 2023. Survival time was defined as the duration from the date of the interview to the date the participant succumbed or the end of the follow-up period. In the present study, age, uric acid (UA) and left atrial diameter (LAD) were found to be independent risk factors for the development of AF in patients diagnosed with COPD. The stepwise logistic regression analysis revealed that age had an odds ratio (OR) of 1.072 [95% confidence interval (CI): 1.019-1.128; P=0.007], UA had an OR of 1.004 (95% CI: 1.001-1.008; P=0.010) and LAD had an OR of 1.195 (95% CI: 1.098-1.301; P<0.001). Univariate and multivariate Cox regression analysis revealed that LAD and UA were independent prognostic factors for long-term mortality in COPD patients with AF. LAD had a hazard ratio (HR) of 1.104 (95% CI: 1.046-1.165; P<0.001) and UA had an HR of 1.004 (95% CI: 1.000-1.008; P=0.042). Based on these findings, predictive nomogram models were developed for AF in COPD patients, which demonstrated good discrimination ability with an area under the curve of 0.886. The prognostic nomogram for COPD patients with AF also showed good predictive accuracy with a concordance index of 0.886 (95% CI: 0.842-0.930). These models can provide valuable information for risk assessment and prognosis evaluation in clinical practice. Age, UA and LAD are independent risk factors for AF in COPD patients. The developed nomogram models provide a reliable tool for predicting AF in COPD patients and for prognosis assessment.