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• Atria make both active and passive contributions throughout the cardiac cycle. • Atrial cardiomyopathy is gaining recognition in various cardiac conditions and is associated with worse prognosis. • Alterations in atrial mechanics are associated with incident heart failure and atrial fibrillation. • Atrial interventions may have adverse subclinical effects on atrial mechanics, which could ultimately result in overt clinical symptoms. • Standardized assessment of atrial mechanics following atrial interventions might allow early detection and prevention of irreversible atrial remodeling. Our comprehension of atrial mechanics, atrial cardiomyopathy and their clinical implications across various cardiovascular conditions has advanced significantly. Atrial interventions can have differing effects on atrial mechanics. With the rapid increase in the use of atrial interventions, it is crucial for investigators and clinicians to acknowledge the potential adverse effects of these interventions on atrial mechanics that might not be clinically significant at the time of interventions. Recognizing the preclinical stage of atrial maladaptation might enable early interventions before the development of irreversible atrial remodeling and clinical manifestation. We review normal atrial function and mechanics, and atrial cardiomyopathy in select cardiovascular conditions. We also summarize and discuss the current evidence of the impact of various atrial interventions on atrial function and mechanics. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Atrial cardiomyopathy (AtCM) has drawn attention as the pathophysiology related to cardiovascular events such as atrial tachyarrhythmia, congestive heart failure, and embolic stroke. As the concept of AtCM is relatively recent, the long-term clinical course of AtCM has not been reported. Case summary Here, we describe a 78-year-old patient diagnosed with end-stage AtCM. He had started to visit our hospital due to paroxysmal atrial fibrillation (AF) and hypertrophic cardiomyopathy over three decades since the age of 45. During follow-up, he experienced cardiogenic embolism and pacemaker implantation due to sick sinus syndrome. At this time, he complained of palpitation due to AF and underwent catheter ablation. Regardless of de novo ablation, left atrial voltage mapping showed ultimately extensive scar in left atrium and pulmonary vein, suggesting that conventional AF ablation strategy was ineffective. From this finding, he was diagnosed with end-stage AtCM. In the review of the previous 12-lead electrocardiogram, P-wave amplitude was decreased, and PR duration was prolonged gradually. We performed only cavotricuspid isthmus ablation and ended the ablation session. After six months, he complained of dyspnoea on effort due to pacing-induced cardiomyopathy. Furthermore, before the cardiac resynchronization therapy with a defibrillator (CRT-D) upgrade, left atrial appendage thrombus was detected even under the administration of apixaban. After thrombolysis with warfarin, CRT-D upgrade the left ventricular ejection fraction was improved. Discussion In this case, the patient slowly developed end-stage AtCM and experienced multiple cardiovascular events related to severe AtCM. We should care for the disease progression of AtCM with vigilance. [ABSTRACT FROM AUTHOR]

Atrial cardiomyopathy and remodeling play pivotal roles in the development of atrial fibrillation (AF) and heart failure (HF), involving complex changes in atrial structure and function. These changes facilitate the progression of AF and HF by creating a dynamic interplay between mechanical stress and electrical disturbances in the heart. Sodium–glucose cotransporter 2 inhibitors (SGLT2is), initially developed for the management of type 2 diabetes, have demonstrated promising cardiovascular benefits, being currently one of the cornerstone treatments in HF management. Despite recent data from randomized clinical trials indicating that SGLT2is may significantly influence atrial remodeling, their overall effectiveness in this context is still under debate. Given the emerging evidence, this review examines the molecular mechanisms through which SGLT2is exert their effects on atrial remodeling, aiming to clarify their potential benefits and limitations. By exploring these mechanisms, this review aims to provide insights into how SGLT2is can be integrated into strategies for preventing the progression of atrial remodeling and HF, as well as the development of AF.

Atrial cardiomyopathy (ACM) represents a novel paradigm in cardiovascular medicine, encompassing structural and functional changes within the atria that contribute to adverse clinical outcomes, notably stroke. This review explores the multifaceted implications of ACM, particularly its relevance independent of atrial fibrillation (AF) and its potential applications in stroke prevention and management. Advancements in imaging modalities, notably speckle-tracking echocardiography, offer valuable insights into atrial remodeling and dysfunction, facilitating early detection of ACM. Markers such as P-wave terminal force, NT-proBNP levels, and left atrial dimensions serve as diagnostic indicators for ACM, aiding in risk stratification in individuals devoid of AF history. Ischemic strokes are one of the most common causes of cardiovascular morbidity and mortality. A significant proportion of patients with ischemic stroke are suspected of embolic stroke without a specific embolic source being found (ESUS). The most recent related clinical trials evaluated tailored anticoagulation strategies in ACM-associated stroke, signaling a shift beyond conventional AF management. In conclusion, ACM emerges as a pivotal concept in stroke prevention, offering opportunities for personalized interventions and refined risk stratification beyond AF.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with significant morbidity and mortality. Managing risk of stroke and AF burden are pillars of AF management. Atrial geometry has long been recognized as a useful measure in achieving these goals. However, traditional diagnostic approaches often overlook the complex spatial dynamics of the atria. This review explores the emerging role of three-dimensional (3D) atrial geometry in the evaluation and management of AF. Advancements in imaging technologies and computational modeling have enabled detailed reconstructions of atrial anatomy, providing insights into the pathophysiology of AF that were previously unattainable. We examine current methodologies for interpreting 3D atrial data, including qualitative, basic quantitative, global quantitative, and statistical shape modeling approaches. We discuss their integration into clinical practice, highlighting potential benefits such as personalized treatment strategies, improved outcome prediction, and informed treatment approaches. Additionally, we discuss the challenges and limitations associated with current approaches, including technical constraints and variable interpretations, and propose future directions for research and clinical applications. This comprehensive review underscores the transformative potential of leveraging 3D atrial geometry in the evaluation and management of AF, advocating for its broader adoption in clinical practice. [ABSTRACT FROM AUTHOR]

[Display omitted] Atrial fibrillation (AF) is the primary cause of ischaemic stroke and transient ischaemic attack (TIA). AF is associated with a high risk of recurrence, which can be reduced using optimal prevention strategies, mainly anticoagulant therapy. The availability of effective prophylaxis justifies the need for a significant, coordinated and thorough transdisciplinary effort to screen for AF associated with stroke. A recent French national survey, initiated and supported by the Société française neurovasculaire (SFNV) and the Société française de cardiologie (SFC), revealed many shortcomings, such as the absence or inadequacy of telemetry equipment in more than half of stroke units, insufficient and highly variable access to monitoring tools, delays in performing screening tests, heterogeneous access to advanced or connected ambulatory monitoring techniques, and a lack of dedicated human resources. The present scientific document has been prepared on the initiative of the SFNV and the SFC with the aim of helping to address the current shortcomings and gaps, to promote efficient and cost-effective AF detection, and to improve and, where possible, homogenize the quality of practice in AF screening among stroke units and outpatient post-stroke care networks. The working group, composed of cardiologists and vascular neurologists who are experts in the field and are nominated by their peers, reviewed the literature to propose statements, which were discussed in successive cycles, and maintained, either by consensus or by vote, as appropriate. The text was then submitted to the SFNV and SFC board members for review. This scientific statement document argues for the widespread development of patient pathways to enable the most efficient AF screening after stroke. This assessment should be carried out by a multidisciplinary team, including expert cardiologists and vascular neurologists. [ABSTRACT FROM AUTHOR]

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Ischemic stroke is a leading cause of morbidity and mortality worldwide. Emerging evidence suggests that left atrial (LA) dysfunction could play a role in the pathophysiology of ischemic stroke, as a possible contributor and as a predictive biomarker. This narrative review details the intricate relationship between LA function, atrial fibrillation (AF), and ischemic stroke. We discuss imaging techniques used to assess LA function, the mechanisms by which impaired LA function may contribute to stroke, and its potential as a prognostic marker of stroke. There is a lack of evidence-based treatments of LA dysfunction in both primary and secondary stroke prevention. This is partly due to the lack of a practical clinical definition and unanswered questions concerning the clinical implications of LA dysfunction in patients without AF. Until such questions are resolved, addressing well-known cardiovascular risk factors, like hypertension and obesity, should be prioritized for preventing AF and ischemic stroke. These risk factors are closely tied to atrial remodeling, emphasizing the importance of targeting primary modifiable factors for preventing future morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background Double-wave macrore-entry is a rare mechanism of atrial tachycardia with limited documentation in the literature. We present a three-dimensional documentation of a double-wave 'typical' atrial flutter in a patient with extensive atrial cardiomyopathy. Case summary A 78-year-old female with a history of atrial cardiomyopathy and dual-chamber pacemaker for sinus node disease presented with palpitations and incessant atrial flutter. Electrophysiological study revealed a regular tachycardia with a cycle length (TCL) of 230 ms, with proximal to distal coronary sinus (CS) activation. Three-dimensional mapping identified two independent wavefronts circulating the cavotricuspid isthmus (CTI), each with a TCL of 460 ms. Cavotricuspid isthmus ablation resulted in conversion into a distinct tachycardia with left atrial roof origin. Linear ablation in this location slowed the TCL to 435 ms with concentric CS activation and another CTI dependent atrial flutter was mapped, this time with only one wavefront of activation. Further ablation with a second, more lateral, line in the CTI led to tachycardia interruption. Given the extensive atrial scarring and high arrhythmic recurrence risk, atrioventricular node ablation was performed. Discussion Double-wave re-entrant tachycardias were primarily observed in experimental models, precipitating acceleration of ventricular and supraventricular tachycardias via extrastimulation. In our case, there is documentation of a spontaneous double-wave of activation around the CTI, representing the first documented double-wave 'typical' atrial flutter. Unlike other cases in the literature, the two wavefronts were equidistant, which resulted in a regular tachycardia with TCL that was half of the single-wave cycle length. Three-dimensional propagation mapping was essential to visualize the two distinct wavefronts. [ABSTRACT FROM AUTHOR]

The identification of the pulmonary veins as a trigger source for atrial fibrillation (AF) has established pulmonary vein isolation (PVI) as a key target for AF ablation. However, PVI alone does not prevent recurrent AF in many patients, and numerous additional ablation strategies have failed to improve on PVI outcomes. This therapeutic limitation may be due, in part, to a failure to identify and intervene specifically on the pro-fibrillatory substrate within the atria and pulmonary veins. In this review paper, we highlight several emerging approaches with clinical potential that target atrial cardiomyopathy—the underlying anatomic, electrical, and/or autonomic disease affecting the atrium—in various stages of practice and investigation. In particular, we consider the evolving roles of risk factor modification, targeting of epicardial adipose tissue, tissue fibrosis, oxidative stress, and the inflammasome, along with aggressive early anti-AF therapy in AF management. Attention to combatting substrate development promises to improve outcomes in AF. [Display omitted] • As a therapeutic target for AF, atrial cardiomyopathy is not addressed by ablation. • Biological and clinical data identify adjunctive approaches to AF management that can improve outcomes. • Further studies personalizing therapy to individual causative factors and mechanistic mediators are needed. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) may be asymptomatic and the extensive monitoring capabilities of cardiac implantable electronic devices (CIEDs) revealed asymptomatic atrial tachi-arrhythmias of short duration (minutes-hours) occurring in patients with no prior history of AF and without AF detection at a conventional surface ECG. Both the terms "AHRE" (Atrial High-Rate Episodes) and subclinical AF were used in a series of prior studies, that evidenced the association with an increased risk of stroke. Two randomized controlled studies were planned in order to assess the risk-benefit profile of anticoagulation in patients with AHRE/subclinical AF: the NOAH and ARTESiA trials. The results of these two trials (6548 patients enrolled, overall) show that the risk of stroke/systemic embolism associated with AHRE/subclinical AF is in the range of 1–1.2 % per patient-year, but with an important proportion of severe/fatal strokes occurring in non-anticoagulated patients. The apparent discordance between ARTESiA and NOAH results may be approached by considering the related study-level meta-analysis, which highlights a consistent reduction of ischemic stroke with oral anticoagulants vs. aspirin/placebo (relative risk [RR] 0.68, 95 % CI 0.50–0.92). Oral anticoagulation was found to increase major bleeding (RR 1.62, 95 % CI 1.05–2.5), but no difference was found in fatal bleeding (RR 0.79, 95 % CI 0.37–1.69). Additionally, no difference was found in cardiovascular death or all-cause mortality. Taking into account these results, clinical decision-making for patients with AHRE/subclinical AF at risk of stroke, according to CHA 2 DS 2 -VASc, can now be evidence-based, considering the benefits and related risks of oral anticoagulants, to be shared with appropriately informed patients. [ABSTRACT FROM AUTHOR]

Atrial cardiomyopathy (ACM) forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. However, generating stable animal models that accurately replicate the entire progression of atrial lesions, particularly the onset of AF, presents significant challenges. In the present study, we found that the isoform of CRE-binding protein modulator (CREM-IbΔC-X), which is involved in the regulation of cardiac development and atrial rhythm, was highly expressed in atrial biopsies from patients with AF. Building upon this finding, we employed CRISPR/Cas9 technology to create a mouse model with cardiac-specific overexpression of CREM-IbΔC-X (referred to as CS-CREM mice). This animal model effectively illustrated the development of ACM through electrophysiological and structural remodelings over time. Proteomics and Chip-qPCR analysis of atrial samples revealed significant upregulation of cell-matrix adhesion and extracellular matrix structural components, alongside significant downregulation of genes related to atrial functions in the CS-CREM mice. Furthermore, the corresponding responses to anti-arrhythmia drugs, i.e. , amiodarone and propafenone, suggested that CS-CREM mice could serve as an ideal in vivo model for drug testing. Our study introduced a novel ACM model with spontaneous AF by cardiac-specifically overexpressing CREM-IbΔC-X in mice, providing valuable insights into the mechanisms and therapeutic targets of ACM. [ABSTRACT FROM AUTHOR]

Atrial cardiomyopathy (ACM) is a relatively new term, and is defined as "any complex of structural, architectural, contractile or electrophysiological changes affecting the atria with the potential to produce clinically relevant manifestations". Heart failure (HF) is one of the etiological factors of atrial cardiomyopathy. However, atrial cardiomyopathy itself worsens and complicates the course of heart failure. In the current review we describe the pathophysiology of ACM in HF with preserved ejection fraction (HFpEF), present the concept of disproportionate left atrial myopathy in HFpEF and depict the role of permanent atrial fibrillation for HF worsening and poor prognosis. [ABSTRACT FROM AUTHOR]

In the past, it has been generally accepted that tachyarrhythmias other than atrial fibrillation (AF) such as atrial premature beats (APB) and atrial tachycardia (AT) are not of great clinical significance. However, with the development of detection methods in recent years, more and more clinical studies have found that the atrial ectopic activities of APB and AT except for AF are associated with the risk of stroke, and may further contribute to increased mortality. Meanwhile, a positive association has also been revealed between the frequency of this kind of atrial yarrhythmias, and incidence of adverse events such as AF and ischemic stroke, which may be mediated by subclinical atrial cardiomyopathy. There is still no clear definition of the clinical threshold for this type of arrhythmia and its excessive supraventricular ectopic activities at present. Therefore, it is essential to make regular detection and management of tachyarrhythmia other than AF by means such as ambulatory electrocardiography and by following standardized process. This article describes the relationship between such atrial arrhythmias and cardiogenic stroke, and introduces the role of detecting such arrhythmias in the assessment of cardiogenic stroke. [ABSTRACT FROM AUTHOR]

Atrial cardiomyopathy is known as an underlying pathophysiological factor in the majority of patients with atrial fibrillation (AF). Left atrial low-voltage areas (LVAs) are reported to coincide with fibrosis and likely represent atrial cardiomyopathy. The purpose of this study was to delineate differences in the long-term prognosis of patients stratified by the size of LVAs. This observational study included 1488 consecutive patients undergoing initial ablation for AF. LVAs were defined as regions with a bipolar peak-to-peak voltage <0.50 mV. The total study population was divided into 3 groups stratified by LVA size: patients with no LVAs (n = 1136); those with small (<20 cm2) LVAs (n = 250) LVAs; and those with extensive (≥20 cm2) LVAs (n = 102). Composite endpoints of death, heart failure, and stroke were followed for up to 5 years. Composite endpoints developed in 105 of 1488 patients (7.1%), and AF recurrence occurred in 410 (27.6%). Composite endpoints developed more frequently in the order of patients with extensive LVAs (19.1%), small LVAs (10.8%), and no LVAs (5.1%) (P for trend <.0001). Multivariable analysis revealed that LVA presence was independently associated with higher incidence of composite endpoints, irrespective of AF recurrence (modified hazard ratio 1.73; 95% confidence interval 1.13–2.64; P =.011) LVA presence and its extent both were associated with poor long-term composite endpoints of death, heart failure, and stroke, irrespective of AF recurrence or other confounders. Underlying atrial cardiomyopathy seems to define a poor prognosis after AF ablation. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • ACM is characterized by histopathological and electrophysiological remodelling. • This remodelling leads to adverse clinical outcomes. • Several factors play a critical role in ACM pathogenesis. • These factors include aging, metabolic disorders, pressure overload and genetics. • Noninvasive clinical tools can characterize ACM. • These tools include electrocardiography, cardiac imaging and serum biomarkers. • The tools are helpful in the prediction of adverse clinical outcomes. • The outcomes include atrial fibrillation, stroke, heart failure and dementia. Atrial cardiomyopathy is defined as any complex of structural, architectural, contractile or electrophysiological changes affecting atria, with the potential to produce clinically relevant manifestations. Most of our knowledge about the mechanistic aspects of atrial cardiomyopathy is derived from studies investigating animal models of atrial fibrillation and atrial tissue samples obtained from individuals who have a history of atrial fibrillation. Several noninvasive tools have been reported to characterize atrial cardiomyopathy in patients, which may be relevant for predicting the risk of incident atrial fibrillation and its related outcomes, such as stroke. Here, we provide an overview of the pathophysiological mechanisms involved in atrial cardiomyopathy, and discuss the complex interplay of these mechanisms, including aging, left atrial pressure overload, metabolic disorders and genetic factors. We discuss clinical tools currently available to characterize atrial cardiomyopathy, including electrocardiograms, cardiac imaging and serum biomarkers. Finally, we discuss the clinical impact of atrial cardiomyopathy, and its potential role for predicting atrial fibrillation, stroke, heart failure and dementia. Overall, this review aims to highlight the critical need for a clinically relevant definition of atrial cardiomyopathy to improve treatment strategies. [ABSTRACT FROM AUTHOR]

Aims Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Methods and results Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. Conclusions Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF. [ABSTRACT FROM AUTHOR]

Background: Fibrotic atrial cardiomyopathy plays an important role in determining the outcome of ablation in patients with atrial fibrillation (AF). Two main methods are being used for the evaluation of fibrosis: voltage-based high-density (HD) electroanatomical mapping (EAM) and late gadolinium enhancement MRI (LGE-MRI). The comparability between both methods in detecting fibrosis has not been systematically investigated. Methods: LGE-MRIs of the left atrium (LA) were performed in 21 patients. LA-fibrosis was evaluated using a custom-designed software generating a 3D-model of the LA. HD-electroanatomical maps were recorded in each patient. After processing the maps and the MRI models by excluding the mitral valve, pulmonary veins, and the left atrial appendage, the LGE areas were measured and compared to the low voltage areas (LVA) in the HD maps using three different cutoff values of 0.5 mV, 0.7 mV, and 1.0 mV. Results: The analysis revealed significant differences between EAM and LGE-MRI in assessing LA-fibrosis at 0.5-mV (for anterior and posterior walls) and 1.0-mV cutoffs (for anterior and posterior wall and septum). However, no significant differences were found between EAM and LGE-MRI when using a 0.7-mV cutoff for all the investigated areas. Conclusions: A voltage cutoff of 0.7 mV provided the best correlation between EAM and LGE MRI for detecting left atrial fibrosis. It supports the idea that a 0.5-mV cutoff may underestimate fibrosis, as areas with local signal voltages between 0.6 and 0.8 mV could also show LGE on MRI. Further research is needed to determine the ideal voltage cutoff for detecting left atrial fibrosis. [ABSTRACT FROM AUTHOR]

BackgroundAtrial fibrillation (AF) triggers atrial remodeling, impacting atrial function and ablation efficacy. This remodeling leads to atrial cardiomyopathy and dilatation, linked to mitral regurgitation, forming atrial functional mitral regurgitation (aFMR). Our study explores the relationship between early-stage-aFMR and the atrial electrical architecture, focusing on left atrial bipolar voltage and low-voltage areas (LVAs) in AF patients.MethodsWe enrolled 282 patients undergoing redo-PVI after AF recurrence post-PVI. Echocardiography was performed prior to ablation, and only patients with no, mild, or mild-to-moderate aFMR were included. Ablation used radiofrequency and a 3D mapping system, with atrial voltage documented on each atrial wall. LVAs were calculated using high-density maps, and patients were followed for 15 months.ResultsSignificant differences in left atrial voltage and LVA extent were observed based on aFMR severity. Patients with aFMR 1 + had significantly lower atrial voltage compared to no-aFMR, but no significant increase in LVAs. Patients with aFMR 2 + showed lower voltage amplitudes in all atrial regions and larger LVAs compared to no-aFMR patients. AF recurrence was significantly higher in the aFMR group (62.9% vs. 48.3%, p = 0.027) within 1 year. aFMR was associated with AF recurrence after adjusting for sex, age, and AF types (HR: 1.517, 95% CI: 1.057–2.184, p = 0.025).ConclusionaFMR in AF patients may indicate progressive atrial remodeling and left atrial cardiomyopathy, characterized by reduced atrial voltage and increased LVAs. aFMR is linked to PVI outcomes, suggesting its consideration in AF therapy decision-making.

Summary: Background: Atrial cardiomyopathy (ACM) is responsible for atrial fibrillation (AF) and thromboembolic events. Diabetes mellitus (DM) is an important risk factor for ACM. However, the potential mechanism between ACM and DM remains elusive. Methods: Atrial tissue samples were obtained from patients diagnosed with AF or sinus rhythm (SR) to assess alterations in NR4A3 expression, and then two distinct animal models were generated by subjecting Nr4a3−/− mice and WT mice to a high-fat diet (HFD) and Streptozotocin (STZ), while db/db mice were administered AAV9-Nr4a3 or AAV9-ctrl. Subsequently, in vivo and in vitro experiments were conducted to assess the impact of NR4A3 on diabetes-induced atrial remodeling through electrophysiological, biological, and histological analyses. RNA sequencing (RNA-seq) and metabolomics analysis were employed to unravel the downstream mechanisms. Findings: The expression of NR4A3 was significantly decreased in atrial tissues of both AF patients and diabetic mice compared to their respective control groups. NR4A3 deficiency exacerbated atrial hypertrophy and atrial fibrosis, and increased susceptibility to pacing-induced AF. Conversely, overexpression of NR4A3 alleviated atrial structural remodeling and reduced AF induction rate. Mechanistically, we confirmed that NR4A3 improves mitochondrial energy metabolism and reduces oxidative stress injury by preserving the transcriptional expression of Sdha, thereby exerting a protective influence on atrial remodeling induced by diabetes. Interpretation: Our data confirm that NR4A3 plays a protective role in atrial remodeling caused by diabetes, so it may be a new target for treating ACM. Funding: This study was supported by the major research program of National Natural Science Foundation of China (NSFC) No: 82370316 (to Q-S. W.), No. 81974041 (to Y-P. W.), and No. 82270447 (to Y-P. W.) and Fundation of Shanghai Hospital Development Center (No. SHDC2022CRD044 to Q-S. W.).

Latent atrial fibrillation (AF), whose substrate is atrial cardiomyopathy (AC), is considered the main potential pathogenetic mechanism of cryptogenic embolic stroke (CES). Early detection of AC allows to intensify the search for AF in such patients.Objective: to compare the characteristics of patients with CES in terms of clinical and anamnestic data, echocardiographic parameters, MRI patterns of infarction foci and disease outcomes depending on the presence of the major markers for AC.Material and methods. We studied 103 patients in the acute phase of CES with a lesion confirmed by MRI data, who were divided into two groups according to the presence (n=17) or absence (n=86) of AC. A comprehensive clinical, laboratory, and instrumental examination was performed and long-term outcomes were assessed. The median follow-up period was 32 months.Results. The incidence of AC in the CES population was 17%; the most common markers were an increase in left atrial volume index and paroxysms of supraventricular tachycardia. Patients with AC-CES were characterised by older age and a two-fold increase in the prevalence of coronary heart disease. Patients with AC-CES were nine times more likely to have a "black artery" symptom on MRI than patients without AC. The predictive accuracy of this clinical pattern was 84%, the sensitivity was 60% and the specificity was 86%. Patients with AC-CES had a significantly higher risk (odds ratio 3.4; 95% confidence interval 1.1–9.9; p=0.023) for a composite outcome that included the development of recurrent ischemic stroke, transient ischemic attack, myocardial infarction or death.Conclusion. AC diagnosed by a combination of echocardiographic and electrocardiographic signs is present in 17% of patients with CES. Patients with AC-CES are characterised by elderly age, the presence of atherosclerosis-associated disease, a specific MRI pattern (the “black artery” symptom) and an unfavourable prognosis during the 2.5-year follow-up period.

Advances in cardiovascular imaging have expanded the scope and precision of rare diagnoses. Handling a patient with a giant left atrium, we focused on the existence and associated factors of “lone giant (left or right) atria” in our clinical setting. The aim of the current study was to establish reasonable cut-off values for the diagnosis of “giant atrium”. Our analysis utilised echocardiography and cardiovascular magnetic resonance (CMR) imaging databases, with the original data re-assessed to ensure consistency and comparability. Four patients met the search criteria, with two cases requiring CMR to confirm the diagnosis of “giant atrium”, correcting the initial echocardiographic assessment. Both echocardiography and CMR excel in the assessment of atrial anatomy, although the superior image quality and multiplanar capabilities of CMR support its preference. In assessing the atrial size, the use of 3D volumetric measurements should replace traditional biplane methods due to the complex anatomy of the atrium. We propose the use of an indexed volume threshold (>120 mL/m2) rather than simple diameter measurements for the diagnosis of “giant atria”. Structural atrial abnormalities appear to correlate with an increased risk of atrial arrhythmias, while potential serious complications such as thromboembolism or compression symptoms require further observation in larger patient cohorts to establish definitive risks.

To investigate the clinical and echocardiographic presentation of dogs with persistent atrial standstill (PAS), identify variables measured at first presentation that could predict their survival, and document the progression of the disease after pacing. Retrospective study of medical records of dogs diagnosed with PAS at three referral hospitals of the United Kingdom over seven years. Twenty-six dogs were diagnosed with PAS during the study period. Median age of the population was three years (range: seven months–12.5 years). The most common clinical sign was syncope (14/26). Twenty-four dogs received artificial pacemakers (PM). Major complications after PM implantation were observed in four dogs (four/24). Serial echocardiographic examinations showed that cardiac dimensions of PAS dogs with left atrial or left ventricular dilation at first presentation did not return to reference range after pacing. Further dilation of the cardiac chambers, recurrence of congestive heart failure (CHF), or development of new episodes of CHF were documented in seven, four, and 10 PAS dogs, respectively, despite pacing. Median survival time for cardiac-related deaths after PM implantation was 1512 days (18–3207). Neither CHF nor echocardiographic variables at presentation predicted survival after PM implantation in PAS dogs. Persistent atrial standstill (PAS) is an uncommon bradyarrhythmia, occurring in young adult dogs. Affected dogs were often presented with syncope. Whilst syncope resolved, cardiac remodeling persisted after PM implantation. Long-term survival was favorable after PM implantation and was not predicted by congestive status or cardiac chamber size at first presentation. [ABSTRACT FROM AUTHOR]

• Left atrial (LA) reservoir strain could be a memory of initial atrial myocardial stress in atrial fibrillation (AF). • LA reservoir strain can be predicted using a combination of clinical, biological, metabolomic, and echocardiographic admission variables. • Improvement in characterization of atrial cardiomyopathy in AF is essential in clinical practice because this could be one of the major causes of stroke and heart failure. We identified clinical, biological, metabolomic, and echocardiographic variables associated with atrial cardiomyopathy. The multivariable approach appears to be superior to predict alteration of LA strain. • Early identification of these factors should be useful to facilitate early management of atrial cardiomyopathy in AF. LA strain could well be an integrator of the multiple determinants of atrial myocardial stress. Left atrial (LA) strain is a simple marker of LA function. The aim of the study was to evaluate the determinants of atrial cardiomyopathy in AF. In this pilot study, we prospectively evaluated clinical, biological, metabolomic and echocardiographic parameters for 85 consecutive patients hospitalized for atrial fibrillation (AF) with restoration of sinus rhythm at 6 months. Eighty-one patients with an analysable LA strain at 6 months were divided into groups according to median reservoir strain: < 23.3% (n = 40) versus ≥ 23.3% (n = 41). Compared to patients with the highest LA strain, patients with lowest LA strain had multiple differences at admission: clinical (older age; more frequent history of AF; more patterns of persistent AF); biological (higher fasting blood glucose levels, glycated haemoglobin, high-sensitivity C-reactive protein, and urea; lower glomerular filtration rate); metabolomic (higher levels of kynurenine, kynurenine/tryptophan, and urea/creatinine; lower levels of arginine and methionine/methionine sulfoxide); and echocardiographic (higher two-dimensional end-systolic LA volume [LAV] indexes; higher three-dimensional end-systolic and end-diastolic LAV and right atrial volume indexes; lower LA and right atrial emptying fractions and three-dimensional right ventricular ejection fraction) (all P < 0.05). Area under the receiver operating characteristic curve to predict LA strain alteration at 6 months was highest for a combined score including clinical, biological, metabolomic and echocardiographic variables at admission (area under the receiver operating characteristic curve 0.871; P < 0.0001). LA reservoir strain could be a memory of initial atrial myocardial stress in AF. It can be predicted using a combination of clinical, biological, metabolomic and echocardiographic admission variables. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

(1) Background: Atrial cardiomyopathy constitutes an intrinsically prothrombotic atrial substrate that may promote atrial fibrillation and thromboembolic events, especially stroke, independently of the arrhythmia. Atrial reservoir strain is the echocardiography marker with the most robust evidence supporting its prognostic utility. The main aim of this study is to identify atrial cardiomyopathy by investigating the association between left atrial dysfunction in echocardiography and P-wave abnormalities in the surface electrocardiogram. (2) Methods: This is a community-based, multicenter, prospective cohort study. A randomized sample of 100 patients at a high risk of developing atrial fibrillation were evaluated using diverse echocardiography imaging techniques, and a standard electrocardiogram. (3) Results: Significant left atrial dysfunction, expressed by a left atrial reservoir strain < 26%, showed a relationship with the dilation of the left atrium (p < 0.001), the left atrial ejection fraction < 50% (p < 0.001), the presence of advanced interatrial block (p = 0.032), P-wave voltage in lead I < 0.1 mV (p = 0.008), and MVP ECG score (p = 0.036). (4) Conclusions: A significant relationship was observed between left atrial dysfunction and the presence of left atrial enlargement and other electrocardiography markers; all of them are non-invasive biomarkers of atrial cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Targeting individual sources identified during atrial fibrillation (AF) has been used as an ablation strategy with varying results. Objective: Aim of this study was to evaluate the relationship between regions of interest (ROIs) from CARTOFINDER (CF) mapping and atrial cardiomyopathy from late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR). Methods: Twenty consecutive patients underwent index catheter ablation for persistent AF (PERS AF). Pre‐processed LGE CMR images were merged with the results from CF mapping to visualize harboring regions for focal and rotational activities. Atrial cardiomyopathy was classified based on the four Utah stages. Results: Procedural success was achieved in all patients (n = 20, 100%). LGE CMR revealed an intermediate amount of 21.41% ± 6.32% for LA fibrosis. ROIs were identified in all patients (mean no ROIs per patient n = 416.45 ± 204.57). A tendency towards a positive correlation between the total amount of atrial cardiomyopathy and the total number of ROIs per patient (regression coefficient, β = 10.86, p =.15) was observed. The degree of fibrosis and the presence of ROIs per segment showed no consistent spatial correlation (posterior: β = 0.36, p‐value (p) =.24; anterior: β = −0.08, p =.54; lateral: β = 0.31, p = 39; septal: β = −0.12; p =.66; right PVs: β = 0.34, p =.27; left PVs: β = 0.07, p =.79; LAA: β = −0.91, p =.12). 12 months AF‐free survival was 70% (n = 14) after ablation. Conclusion: The presence of ROIs from CF mapping was not directly associated with the extent and location of fibrosis. Further studies evaluating the relationship between focal and rotational activity and atrial cardiomyopathy are mandatory. [ABSTRACT FROM AUTHOR]

The detection of atrial high rate episodes (AHREs) as well as subclinical atrial fibrillation (SCAF) using cardiac implantable electronic devices increases proportionally to the length of the patients' follow-up period. The occurrence of AHREs nowadays is shown in massively increasing events during routine arrhythmologic follow ups. Almost 35% of patients with an implanted pacemaker have at least one AHRE over a period of 2.5 years. The significance and risk of given episodes is constantly being explored and evolving over time. According to current knowledge, we know that AHREs represent not only the risk of paroxysmal atrial fibrillation, but also a separate independent risk of stroke, and are also associated with an increase in cardiovascular morbidity and mortality. A holistic approach to AHREs emphasizes the importance of the fibrotic process as the main triggering cause of the so-called fibrotic atrial cardiomyopathy and associated thromboembolism. Fig. 1, Ref. 24, on-line full text (Free, PDF) www.cardiologyletters.sk. [ABSTRACT FROM AUTHOR]

Background and aims: Left atrial (LA) enlargement has been repeatedly shown to be associated with the diagnosis of atrial fibrillation (AF). In clinical practice, several parameters are available to determine LA enlargement: LA diameter index (LADI), LA area index (LAAI), or LA volume index (LAVI). We investigated the predictive power of these individual LA parameters for AF in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: LAETITIA is a retrospective observational study that reflects the clinical reality of acute stroke care in Germany. Consecutive patient cases with acute ischemic cerebrovascular event (CVE) in 2019 and 2020 were identified from the Mannheim stroke database. Predictive power of each LA parameter was determined by the area under the curve (AUC) of receiver operating characteristic curves. A cutoff value was determined. A multiple logistic regression analysis was performed to confirm the strongest LA parameter as an independent predictor of AF in patients with acute ischemic CVE. Results: A total of 1,910 patient cases were included. In all, 82.0% of patients had suffered a stroke and 18.0% had a TIA. Patients presented with a distinct cardiovascular risk profile (reflected by a CHA2DS2-VASc score ≥2 prior to hospital admission in 85.3% of patients) and were moderately affected on admission [median NIHSS score 3 (1; 8)]. In total, 19.5% of patients had pre-existing AF, and 8.0% were newly diagnosed with AF. LAAI had the greatest AUC of 0.748, LADI of 0.706, and LAVI of 0.719 (each p < 0.001 vs. diagonal line; AUC-LAAI vs. AUC-LADI p = 0.030, AUC-LAAI vs. AUC-LAVI p = 0.004). LAAI, increasing NIHSS score on admission, and systolic heart failure were identified as independent predictors of AF in patients with acute ischemic CVE. To achieve a clinically relevant specificity of 70%, a cutoff value of ≥10.3 cm²/m² was determined for LAAI (sensitivity of 69.8%). Conclusion: LAAI revealed the best prediction of AF in patients with acute ischemic CVE and was confirmed as an independent risk factor. An LAAI cutoff value of 10.3 cm²/m² could serve as an inclusion criterion for intensified AF screening in patients with embolic stroke of undetermined source in subsequent studies. [ABSTRACT FROM AUTHOR]

Aims Recurrence of arrhythmia after catheter ablation of atrial fibrillation (AF) in the form of atypical atrial flutter (AFL) is common among a significant number of patients and often requires redo ablation with limited success rates. Identifying patients at high risk of AFL after AF ablation could aid in patient selection and personalized ablation approach. The study aims to assess the relationship between pre-existing atrial cardiomyopathy and the occurrence of AFL following AF ablation. Methods and results We analysed a cohort of 1007 consecutive AF patients who underwent catheter ablation and were included in a prospective registry. Patients who did not have baseline cardiac magnetic resonance imaging and late gadolinium enhancement (LGE-CMR) or did not experience any recurrences were excluded. A total of 166 patients were included gathering 56 patients who underwent re-ablation due to AFL recurrences and 110 patients who underwent re-ablation due to AF recurrences (P = 0.11). A multiparametric assessment of atrial cardiomyopathy was based on basal LGE-CMR, including left atrial (LA) volume, LA sphericity, and global and segmental LA fibrosis using semiautomated post-processing software. Out of the initial cohort of 1007 patients, AFL and AF occurred in 56 and 110 patients, respectively. An age higher than 65 [odds ratio (OR) = 5.6, 95% confidence interval (CI): 2.2–14.4], the number of previous ablations (OR = 3.0, 95% CI: 1.2–7.8), and the management of ablation lines in the index procedure (OR = 2.5, 95% CI: 1.0–6.3) were independently associated with AFL occurrence. Furthermore, several characteristics assessed by LGE-CMR were identified as independent predictors of AFL recurrence after the index ablation for AF, such as enhanced LA sphericity (OR = 1.3, 95% CI: 1.1–1.6), LA global fibrosis (OR = 1.03, 95% CI: 1.01–1.07), and increased fibrosis in the lateral wall (OR = 1.03, 95% CI: 1.01–1.04). Conclusion Advanced atrial cardiomyopathy assessed by LGE-CMR, such as increased LA sphericity, global LA fibrosis, and fibrosis in the lateral wall, is independently associated with arrhythmia recurrence in the form of AFL following AF ablation. [ABSTRACT FROM AUTHOR]

Aims Electro-anatomical voltage, conduction velocity (CV) mapping, and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) have been correlated with atrial cardiomyopathy (ACM). However, the comparability between these modalities remains unclear. This study aims to (i) compare pathological substrate extent and location between current modalities, (ii) establish spatial histograms in a cohort, (iii) develop a new estimated optimized image intensity threshold (EOIIT) for LGE-MRI identifying patients with ACM, (iv) predict rhythm outcome after pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF). Methods and results Thirty-six ablation-naive persistent AF patients underwent LGE-MRI and high-definition electro-anatomical mapping in sinus rhythm. Late gadolinium enhancement areas were classified using the UTAH, image intensity ratio (IIR >1.20), and new EOIIT method for comparison to low-voltage substrate (LVS) and slow conduction areas <0.2 m/s. Receiver operating characteristic analysis was used to determine LGE thresholds optimally matching LVS. Atrial cardiomyopathy was defined as LVS extent ≥5% of the left atrium (LA) surface at <0.5 mV. The degree and distribution of detected pathological substrate (percentage of individual LA surface are) varied significantly (P < 0.001) across the mapping modalities: 10% (interquartile range 0–14%) of the LA displayed LVS <0.5 mV vs. 7% (0–12%) slow conduction areas <0.2 m/s vs. 15% (8–23%) LGE with the UTAH method vs. 13% (2–23%) using IIR >1.20, with most discrepancies on the posterior LA. Optimized image intensity thresholds and each patient's mean blood pool intensity correlated linearly (R 2 = 0.89, P < 0.001). Concordance between LGE-MRI-based and LVS-based ACM diagnosis improved with the novel EOIIT applied at the anterior LA [83% sensitivity, 79% specificity, area under the curve (AUC): 0.89] in comparison to the UTAH method (67% sensitivity, 75% specificity, AUC: 0.81) and IIR >1.20 (75% sensitivity, 62% specificity, AUC: 0.67). Conclusion Discordances in detected pathological substrate exist between LVS, CV, and LGE-MRI in the LA, irrespective of the LGE detection method. The new EOIIT method improves concordance of LGE-MRI-based ACM diagnosis with LVS in ablation-naive AF patients but discrepancy remains particularly on the posterior wall. All methods may enable the prediction of rhythm outcomes after PVI in patients with persistent AF. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is strongly associated with stroke risk, but an association by itself does not necessarily imply causation. The question remains whether AF is a risk factor for stroke and whether treatment that reduces the severity of AF will also reduce the burden of stroke. On the other hand, it is possible that AF is a risk marker associated with atrial insufficiency, in which structural and electrical atrial remodeling coexist, leading to the clinical manifestations of AF and the risk of stroke simultaneously. Atrial fibrillation and stroke are inextricably linked to the classic Virchow pathophysiology, which explains thromboembolism as blood stasis in a fibrillating left atrium. This concept has been reinforced by the proven efficacy of oral anticoagulants for the prevention of stroke in AF. However, a number of observations showing that the presence of AF is neither necessary nor sufficient for stroke cast doubt on the causal role of AF in vascular brain injury. The growing recognition of the role of atrial cardiomyopathy and the atrial substrate in the development of stroke associated with AF, as well as stroke without AF, has led to a rethinking of the pathogenetic model of cardioembolic stroke. A number of recent studies have shown that AF is a direct cause of stroke. Studies in which cardiac implantable devices have been used to collect data on pre-stroke AF do not appear to show a direct time relationship. The presence of AF is neither necessary nor sufficient for stroke, which casts doubt on the causal role of AF in cerebrovascular injury. Known risk factors for stroke in the presence of AF are also recognized risk factors for ischemic stroke, regardless of the presence of AF. The risk of stroke in patients with AF in the absence of risk factors differs little from that in patients without AF. This work is devoted to an attempt to answer the question whether AF is a marker or a risk factor for ischemic stroke.

Background Atrial cardiomyopathy (atCM) is an emerging prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy, and capillary density are hallmarks of atCM. The contribution of etiological factors and atrial fibrillation (AF) to the development of differential atCM phenotypes has not been quantified. This study aimed to evaluate the association between histological features of atCM and the clinical phenotype. Methods and Results We examined left atrial (LA, n=95) and right atrial (RA, n=76) appendages from a European cohort of patients undergoing cardiac surgery. Quantification of histological atCM features was performed following wheat germ agglutinin/CD31/vimentin staining. The contributions of AF, heart failure, sex, and age to histological characteristics were determined with multiple linear regression models. Persistent AF was associated with increased endomysial fibrosis (LA: +1.13±0.47 μm, P=0.038; RA: +0.94±0.38 μm, P=0.041), whereas total extracellular matrix content was not. Men had larger cardiomyocytes (LA: +1.92±0.72 μm, P

Background and aimsLeft atrial (LA) enlargement has been repeatedly shown to be associated with the diagnosis of atrial fibrillation (AF). In clinical practice, several parameters are available to determine LA enlargement: LA diameter index (LADI), LA area index (LAAI), or LA volume index (LAVI). We investigated the predictive power of these individual LA parameters for AF in patients with acute ischemic stroke or transient ischemic attack (TIA).MethodsLAETITIA is a retrospective observational study that reflects the clinical reality of acute stroke care in Germany. Consecutive patient cases with acute ischemic cerebrovascular event (CVE) in 2019 and 2020 were identified from the Mannheim stroke database. Predictive power of each LA parameter was determined by the area under the curve (AUC) of receiver operating characteristic curves. A cutoff value was determined. A multiple logistic regression analysis was performed to confirm the strongest LA parameter as an independent predictor of AF in patients with acute ischemic CVE.ResultsA total of 1,910 patient cases were included. In all, 82.0% of patients had suffered a stroke and 18.0% had a TIA. Patients presented with a distinct cardiovascular risk profile (reflected by a CHA2DS2-VASc score ≥2 prior to hospital admission in 85.3% of patients) and were moderately affected on admission [median NIHSS score 3 (1; 8)]. In total, 19.5% of patients had pre-existing AF, and 8.0% were newly diagnosed with AF. LAAI had the greatest AUC of 0.748, LADI of 0.706, and LAVI of 0.719 (each p < 0.001 vs. diagonal line; AUC-LAAI vs. AUC-LADI p = 0.030, AUC-LAAI vs. AUC-LAVI p = 0.004). LAAI, increasing NIHSS score on admission, and systolic heart failure were identified as independent predictors of AF in patients with acute ischemic CVE. To achieve a clinically relevant specificity of 70%, a cutoff value of ≥10.3 cm2/m2 was determined for LAAI (sensitivity of 69.8%).ConclusionLAAI revealed the best prediction of AF in patients with acute ischemic CVE and was confirmed as an independent risk factor. An LAAI cutoff value of 10.3 cm2/m2 could serve as an inclusion criterion for intensified AF screening in patients with embolic stroke of undetermined source in subsequent studies.

Serum C-peptide exhibits various biological activities. The relationship between C-peptide and atrial cardiomyopathy remains unknown. We aimed to investigate the association between C-peptide level and atrial cardiomyopathy in nondiabetic adults. Our study enrolled 4578 participants without diagnosed diabetes from the Third National Health and Nutrition Examination Survey (NHANES III). Atrial cardiomyopathy was defined as a deep terminal negative P wave in V1 below − 100 µV (more negative), according to the electrocardiogram. The participants were categorized into low C-peptide (≤ 1.46 nmol/L) and high C-peptide (> 1.46 nmol/L) groups, according to the receiver operating characteristic analysis. Odds ratio (OR) and 95% confidence interval (CI) for the association between C-peptide level and atrial cardiomyopathy were generated using multivariate logistic regression analysis. The prevalence of atrial cardiomyopathy was higher in the high C-peptide group than in the low C-peptide group (5.62% vs. 2.31%, P < 0.001, respectively). Multivariate logistic regression analysis showed that participants in the high C-peptide group had a 3.60-fold (95% CI 1.81–6.99) higher risk of atrial cardiomyopathy than those in the low C-peptide group. Per standard deviation increase in C-peptide was linked to a 1.20-fold (95% CI 1.00–1.41) higher risk in atrial cardiomyopathy. High C-peptide level might be an independent risk factor for atrial cardiomyopathy in nondiabetic adults. [ABSTRACT FROM AUTHOR]

The objective of the study was to examine the joint associations of albuminuria and electrocardiographic left atrial abnormality (ECG-LAA) with incident atrial fibrillation (AF) and whether this relationship varies by race. This analysis included 6670 participants free of clinical cardiovascular disease (CVD), including atrial fibrillation (AF), from the Multi-Ethnic Study of Atherosclerosis. ECG-LAA was defined as P-wave terminal force in V1 [PTFV1] >5000 μV × ms. Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥30 mg/g. Incident AF events through 2015 were ascertained from hospital discharge records and study-scheduled electrocardiograms. Cox proportional hazard models were used to examine the association of "no albuminuria + no ECG-LAA (reference)", "isolated albuminuria", "isolated ECG-LAA" and "albuminuria + ECG-LAA" with incident AF. Over a median follow-up of 13.8 years, 979 incident cases of AF occurred. In adjusted models, the concomitant presence of ECG-LAA and albuminuria was associated with a higher risk of AF than either ECG-LAA or albuminuria in isolation (HR (95% CI): 2.43 (1.65–3.58), 1.33 (1.05–1.69), and 1.55 (1.27–1.88), respectively (interaction p-value = 0.50). Effect modification by race was observed with a 4-fold greater AF risk in Black participants with albuminuria + ECG-LAA (HR (95%CI): 4.37 (2.38–8.01) but no significant association in White participants (HR (95% CI) 0.60 (0.19–1.92) respectively; (interaction p-value for race x albuminuria-ECG-LAA combination = 0.05). Concomitant presence of ECG-LAA and albuminuria confers a higher risk of AF compared to either one in isolation with a stronger association in Blacks than Whites. • Impact of combination of albuminuria and ECG left atrial abnormality (ECG-LAA) on atrial fibrillation (AF) risk is unknown. • Concomitant presence of albuminuria and ECG-LAA is associated with a greater risk of AF than each predictor in isolation. • Only Black individuals with concomitant albuminuria and ECG-LAA have a higher risk of incident AF. • These findings raise the possibility of a differential mechanistic pathway to AF according to race-ethnicity. [ABSTRACT FROM AUTHOR]

Background and purpose: Growing evidence suggests that atrial cardiomyopathy may play an essential role in thrombosis and ischemic stroke. The aim of this systematic review and meta-analysis was to quantify the values of cardiomyopathy markers for predicting ischemic stroke risk. Methods: PubMed, Embase, and the Cochrane Library were searched for longitudinal cohort studies evaluating the association between cardiomyopathy markers and incident ischemic stroke risk. Results: We included 25 cohort studies examining electrocardiographic, structural, functional, and serum biomarkers of atrial cardiomyopathy involving 262,504 individuals. P-terminal force in the precordial lead V1 (PTFV1) was found to be an independent predictor of ischemic stroke as both a categorical variable (HR 1.29, CI 1.06–1.57) and a continuous variable (HR 1.14, CI 1.00–1.30). Increased maximum P-wave area (HR 1.14, CI 1.06–1.21) and mean P-wave area (HR 1.12, CI 1.04–1.21) were also associated with an increased risk of ischemic stroke. Left atrial (LA) diameter was independently associated with ischemic stroke as both a categorical variable (HR 1.39, CI 1.06–1.82) and a continuous variable (HR 1.20, CI 1.06–1.35). LA reservoir strain independently predicted the risk of incident ischemic stroke (HR 0.88, CI 0.84–0.93). N-terminal pro-brain natriuretic peptide (NT-proBNP) was also associated with incident ischemic stroke risk, both as a categorical variable (HR 2.37, CI 1.61–3.50) and continuous variable (HR 1.42, CI 1.19–1.70). Conclusion: Atrial cardiomyopathy markers, including electrocardiographic markers, serum markers, LA structural and functional markers, can be used to stratify the risk of incident ischemic stroke. [ABSTRACT FROM AUTHOR]

This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors, such as valvular disease leading to atrial structural and functional remodeling due to pressure and volume overload. Atrial enlargement and dysfunction can trigger atrial tachyarrhythmia. The complex interaction between valvular disease and atrial cardiomyopathy creates a vicious cycle of aggravating atrial enlargement, dysfunction, and valvular disease severity. Furthermore, atrial remodeling and arrhythmia can predispose to atrial thrombus formation and stroke. The underlying pathomechanism of atrial myopathy involves molecular, cellular, and subcellular alterations resulting in chronic inflammation, atrial fibrosis, and electrophysiological changes. Atrial dysfunction has emerged as an essential determinant of outcomes in valvular disease and heart failure. Despite its predictive value, the detection of atrial fibrosis and dysfunction is challenging and is not included in the clinical routine. Transthoracic echocardiography and cardiac magnetic resonance imaging are the main diagnostic tools for atrial cardiomyopathy. Recently published data have revealed that both left atrial volumes and functional parameters are independent predictors of cardiovascular events in valvular disease. The integration of atrial function assessment in clinical practice might help in early cardiovascular risk estimation, promoting early therapeutic intervention in valvular disease. [ABSTRACT FROM AUTHOR]

Abstract Atrial cardiomyopathy refers to structural and electrical remodelling of the atria, which can lead to impaired mechanical function. While historical studies have implicated atrial fibrillation as the leading cause of cardioembolic stroke, atrial cardiomyopathy may be an important, underestimated contributor. To date, the relationship between atrial cardiomyopathy, atrial fibrillation, and cardioembolic stroke remains obscure. This review summarizes the pathogenesis of atrial cardiomyopathy, with a special focus on neurohormonal and inflammatory mechanisms, as well as the role of adipose tissue, especially epicardial fat in atrial remodelling. It reviews the current evidence implicating atrial cardiomyopathy as a cause of embolic stroke, with atrial fibrillation as a lagging marker of an increased thrombogenic atrial substrate. Finally, it discusses the potential of antithrombotic therapy in embolic stroke with undetermined source and appraises the available diagnostic techniques for atrial cardiomyopathy, including imaging techniques such as echocardiography, computed tomography, and magnetic resonance imaging as well as electroanatomic mapping, electrocardiogram, biomarkers, and genetic testing. More prospective studies are needed to define the relationship between atrial cardiomyopathy, atrial fibrillation, and embolic stroke and to establish a prompt diagnosis and specific treatment strategies in these patients with atrial cardiomyopathy for the secondary and even primary prevention of embolic stroke.

Background The frequency of cryptogenic stroke (CS) is about 30% of all cases of ischemic stroke (IS). Patients with CS represent a heterogeneous group of patients and require an individualized approach to antithrombotic therapy for secondary prevention. The frequency of development of repeated acute cerebrovascular events in patients with CS is 4.5% per year, which exceeds this indicator in patients with an established pathogenetic variant of IS. Until recently, the dominant point of view, suggesting that the main cause of CS is paroxysmal atrial fibrillation (AF) and for the secondary prevention of IS in this cohort of patients, oral anticoagulants may be more effective than antiplatelet agents, has not been confirmed. The causal relationship between IS and AF is currently not fully understood. Apparently, AF serves as a marker of atrial cardiomyopathy, which is the direct cause of IS.Aim of study Raising the awareness of neurologists about the causes, pathogenetic mechanisms of development and methods for diagnosing IS in patients with atrial cardiomyopathy.Material and methods To achieve this aim, the results of scientific studies on atrial cardiomyopathy as a risk factor for CS were analyzed. The literature search was carried out in electronic search systems Scopus, eLibrary, PubMed using the keywords: ischemic stroke, cryptogenic stroke, atrial cardiomyopathy, pathogenesis of ischemic stroke. Scientific articles published between 1957 and 2021 were selected to be analyzed. And 36% of the analyzed papers on the topic of CS were published no more than 5 years ago.Conclusion The cumulative evidence suggests that atrial fibrillation is not the only cause of embolic events in patients with evidence of atrial dysfunction. Atrial cardiomyopathy can be the cause of thromboembolic syndrome and cryptogenic stroke, even in the absence of atrial fibrillation, therefore, the latter should be considered as a common manifestation of the underlying atrial cardiomyopathy. Since the majority of cardiac thrombi in patients with atrial fibrillation originate in the left atrium, it is likely that patients with atrial cardiomyopathy and cryptogenic stroke represent a group of patients who may be indicated for anticoagulant therapy as a secondary prevention of ischemic stroke and systemic embolism. However, this hypothesis needs to be confirmed.

Aims To evaluate the extent of left atrial (LA) fibrosis in patients with a recent stroke without atrial fibrillation and controls without established cardiovascular disease. Methods and results This prospectively designed study used cardiac magnetic resonance to detect LA late gadolinium enhancement as a proxy for LA fibrosis. Between 2019 and 2021, we consecutively included 100 patients free of atrial fibrillation with recent ischaemic stroke (<30 days) and 50 age- and sex-matched controls. LA fibrosis assessment was achieved in 78 patients and 45 controls. Blinded to the cardiac magnetic resonance results, strokes were adjudicated according to modified Trial of Org 10172 in Acute Stroke Treatment classification as undetermined aetiology (n = 42) or as attributable to large- or small-vessel disease (n = 36). Patients with stroke had a larger extent of LA fibrosis [6.9%, interquartile range (IQR) 3.6–15.4%] than matched controls (4.2%, IQR 2.3–7.5%; P = 0.007). No differences in LA fibrosis were observed between patients with stroke of undetermined aetiology and those with large- or small-vessel disease (6.6%, IQR 3.8–16.0% vs. 6.9%, IQR 3.4–14.6%; P = 0.73). Conclusion LA fibrosis was more extensive in patients with stroke than in age- and sex-matched controls. A similar extent of LA fibrosis was observed in patients with stroke of undetermined aetiology and stroke classified as attributable to large- or small-vessel disease. Our findings suggest that LA structural abnormality is more frequent in patients with stroke than in controls independent of aetiological classification. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine the prevalence of abnormal P‐wave parameters in patients with thrombus and/or spontaneous echo contrast (SEC) in the left atrial appendage (LAA), and to identify P‐wave parameters particularly associated with thrombus and SEC formation. Hypothesis: We presume a significant relationship of P‐wave parameters with thrombi and SEC. Methods: All patients in whom a thrombus or SEC was detected in the LAA on transoesophageal echocardiography were included in this study. Patients at risk (CHA2DS2‐VASc Score ≥3) and routine transoesophageal echocardiography to exclude thrombi served as the control group. A detailed ECG analysis was performed. Results: Of a total of 4062 transoesophageal echocardiographies, thrombi and SEC were detected in 302 patients (7.4%). Of these patients, 27 (8.9%) presented with sinus rhythm. The control group included 79 patients. There was no difference in mean CHA2DS2‐VASc score in the two groups (p =.182). A high prevalence of abnormal P‐wave parameters was detected in patients with thrombus/SEC. Indicators for the presence of thrombi or SEC in the LAA were P‐wave duration >118 ms (Odds ratio (OR) 3.418, Confidence interval (CI) 1.522–7.674, p <.001), P‐wave dispersion >40 ms (OR 2.521, CI 1.390–4.571, p <.001) and advanced interatrial block (OR 1.431, CI 1.033–1.984, p =.005). Conclusion: Our study revealed that several P‐wave parameters are associated with thrombi and SEC in the LAA. The results may help identify patients who are at particularly high risk for thromboembolic events (e.g., in patients with embolic stroke of undetermined source). [ABSTRACT FROM AUTHOR]

IntroductionAtrial fibrillation (AF) is associated with an increased risk of stroke, often caused by thrombi that form in the left atrium (LA), and especially in the left atrial appendage (LAA). The underlying mechanism is not fully understood but is thought to be related to stagnant blood flow, which might be present despite sinus rhythm. However, measuring blood flow and stasis in the LAA is challenging due to its small size and low velocities. We aimed to compare the blood flow and stasis in the left atrium of paroxysmal AF patients with controls using computational fluid dynamics (CFD) simulations.MethodsThe CFD simulations were based on time-resolved computed tomography including the patient-specific cardiac motion. The pipeline allowed for analysis of 21 patients with paroxysmal AF and 8 controls. Stasis was estimated by computing the blood residence time.Results and DiscussionResidence time was elevated in the AF group (p

ObjectiveTo characterize the cardiac phenotype associated with the novel pathogenic variant (c.1526del) of LMNA gene, which we identified in a large, six-generation family.Methods and ResultsA family tree was constructed. The clinical data of living and deceased family members were collected. DNA samples from 7 family members were analyzed for LMNA mutations using whole-exome high-throughput sequencing technology. The clinical presentation of pathogenic variant carriers was evaluated. In this six-generation family (n = 67), one member experienced sudden death at the age of 40-years-old. Three pathogenic variant carriers were identified to possess a novel heterozygous deletion mutation in LMNA gene (HGVS: NM_170707.4, c.1526del) located at exon 9 of LMNA chr1:156137145, which creates a premature translational stop signal (p.Pro509Leufs*39) in the LMNA gene and results in an mutant lamin A protein product. The main symptoms of the pathogenic variant carriers were palpitation, fatigue, and syncope, which typically occurred around 20-years-old. AV-conduction block and non-sustained ventricular tachycardia were the first signs of disease and would rapidly progress to atrial standstill around 30-years-old. Significant right atrial enlargement and bicuspid aortic valve malformation was also commonly seen in patients who carried this pathogenic variant.ConclusionThe pathogenic variant of c.1526del p.P509Lfs*39 was a frameshift deletion located at exon 9 of LMNA chr1:156137145 and causes severe right atrial enlargement, sick sinus syndrome, atrial standstill, ventricular tachycardia, and bicuspid aortic valve malformation. Our findings expand the phenotypic spectrum of novel LMNA gene mutations.

BackgroundThe association of electrocardiographic (ECG) markers of atrial cardiomyopathy with heart failure (HF) and its subtypes is unclear.MethodsThis analysis included 6,754 participants free of clinical cardiovascular disease (CVD), including atrial fibrillation (AF), from the Multi-Ethnic Study of Atherosclerosis. Five ECG markers of atrial cardiomyopathy (P-wave terminal force in V1 [PTFV1], deep-terminal negativity in V1 [DTNV1], P-wave duration [PWD], P-wave axis [PWA], advanced intra-atrial block [aIAB]) were derived from digitally recorded electrocardiograms. Incident HF events through 2018 were centrally adjudicated. An ejection fraction (EF) of 50% at the time of HF was used to classify HF as HF with reduced EF (HFrEF), HF with preserved EF (HFpEF), or unclassified HF. Cox proportional hazard models were used to examine the associations of markers of atrial cardiomyopathy with HF. The Lunn-McNeil method was used to compare the associations in HFrEF vs. HFpEF.Results413 HF events occurred over a median follow-up of 16 years. In adjusted models, abnormal PTFV1 (HR (95%CI): 1.56(1.15–2.13), abnormal PWA (HR (95%CI):1.60(1.16–2.22), aIAB (HR (95%CI):2.62(1.47–4.69), DTNPV1 (HR (95%CI): 2.99(1.63–7.33), and abnormal PWD (HR (95%CI): 1.33(1.02–1.73), were associated with increased HF risk. These associations persisted after further adjustments for intercurrent AF events. No significant differences in the strength of association of each ECG predictor with HFrEF and HFpEF were noted.ConclusionsAtrial cardiomyopathy defined by ECG markers is associated with HF, with no differences in the strength of association between HFrEF and HFpEF. Markers of atrial Cardiomyopathy may help identify individuals at risk of developing HF.

Objectives: To determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy. Background: We have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial fibrosis, standstill, and dysrhythmia. However, the underlying pathogenic mechanisms remain unclear. Methods and results: Rats subjected to knock-in of a pathogenic MYL4 mutant (p.E11K) developed fibrotic atrial cardiomyopathy. Proteome analysis and single-cell RNA sequencing indicate enrichment of autophagy pathways in mutant-MYL4 atrial dysfunction. Immunofluorescence and electron microscopy revealed undegraded autophagic vesicles accumulated in MYL4p.E11K rat atrium. Next, we identified that dysfunctional MYL4 protein impairs autophagy flux in vitro and in vivo. Cardiac lysosome positioning and mobility were regulated by MYL4 in cardiomyocytes, which affected lysosomal acidification and maturation of lysosomal cathepsins. We then examined the effects of MYL4 overexpression via adenoviral gene-transfer on atrial cardiomyopathy induced by MYL4 mutation: MYL4 protein overexpression attenuated atrial structural remodeling and autophagy dysfunction. Conclusions: MYL4 regulates autophagic flux in atrial cardiomyocytes via lysosomal mobility. MYL4 overexpression attenuates MYL4 p.E11K induced fibrotic atrial cardiomyopathy, while correcting autophagy and lysosomal function. These results provide a molecular basis for MYL4-mutant induced fibrotic atrial cardiomyopathy and identify a potential biological-therapy approach for the treatment of atrial fibrosis.