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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.

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.

Changes in atrial size and function have historically been considered a surrogate marker of ventricular dysfunction. However, it is now recognized that atrial cardiomyopathy (ACM) may also occur as a primary myocardial disorder. Emerging evidence that ACM is a major risk factor for atrial fibrillation, heart failure, and thromboembolic stroke, has highlighted the significance of this disorder and the need for better assessment of atrial metrics in clinical practice. Key barriers in this regard include a lack of standardized criteria or hierarchy for the diagnosis of ACM and lack of consensus for the most accurate phenotyping methods. In this article we review existing literature on ACM, with a focus on current and future non-invasive imaging methods for detecting abnormalities of atrial structure and function. We discuss the relative advantages and disadvantages of transthoracic echocardiography and cardiac magnetic resonance imaging for assessing a range of parameters, including atrial size and contractile function, strain, tissue characteristics, and epicardial adipose tissue. We will also present the potential application of novel imaging methods such as sphericity index and four- or five-dimensional flow.

IntroductionOutcomes of catheter ablation for non-paroxysmal atrial fibrillation (AF) remain suboptimal. Non-invasive stratification of patients based on the presence of atrial cardiomyopathy (ACM) could allow to identify the best responders to pulmonary vein isolation (PVI).MethodsObservational multicentre retrospective study in patients undergoing cryoballoon-PVI for non-paroxysmal AF. The duration of amplified P-wave (APW) was measured from a digitally recorded 12-lead electrocardiogram during the procedure. If patients were in AF, direct-current cardioversion was performed to allow APW measurement in sinus rhythm. An APW cut-off of 150 ms was used to identify patients with significant ACM. We assessed freedom from arrhythmia recurrence at long-term follow-up in patients with APW ≥ 150 ms vs. APW

AimThis study sought to develop and validate diagnostic models to identify individuals with atrial fibrillation (AF) using amplified sinus-p-wave analysis.MethodsA total of 1,492 patients (491 healthy controls, 499 with paroxysmal AF and 502 with persistent AF) underwent digital 12-lead-ECG recording during sinus rhythm. The patient cohort was divided into training and validation set in a 3:2 ratio. P-wave indices (PWI) including duration of standard p-wave (standard PWD; scale at 10 mm/mV, sweep speed at 25 mm/s) and amplified sinus-p-wave (APWD, scale at 60–120 mm/mV, sweep speed at 100 mm/s) and advanced inter-atrial block (aIAB) along with other clinical parameters were used to develop diagnostic models using logistic regression. Each model was developed from the training set and further tested in both training and validation sets for its diagnostic performance in identifying individuals with AF.ResultsCompared to standard PWD (Reference model), which achieved an AUC of 0.637 and 0.632, for training and validation set, respectively, APWD (Basic model) importantly improved the accuracy to identify individuals with AF (AUC = 0.86 and 0.866). The PWI-based model combining APWD, aIAB and body surface area (BSA) further improved the diagnostic performance for AF (AUC = 0.892 and 0.885). The integrated model, which further combined left atrial diameter (LAD) with parameters of the PWI-based model, achieved optimal diagnostic performance (AUC = 0.916 and 0.902).ConclusionAnalysis of amplified p-wave during sinus rhythm allows identification of individuals with atrial fibrillation.

BackgroundProgressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy (ACM) and the transition from paroxysmal to persistent atrial fibrillation (AF). We sought to identify the anatomical/structural and electrophysiological factors involved in atrial remodeling that promote AF persistency.MethodsConsecutive patients with paroxysmal (n = 134) or persistent (n = 136) AF who presented for their first AF ablation procedure were included. Patients underwent left atrial (LA) high-definition mapping (1,835 ± 421 sites/map) during sinus rhythm (SR) and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical mapping and non-invasive baseline data were extracted encompassing four main categories: (1) LA size, (2) extent of low-voltage-substrate (LVS), (3) LA voltages and (4) bi-atrial conduction time as identified by the duration of amplified P-wave (APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness. In addition, HATCH score and C2HEST score were also evaluated for their performance in identification of AF persistency.ResultsIn training and validation sets, APWD (threshold 151 ms), LA volume (LAV, threshold 94 mL), bipolar LVS area < 1.0 mV (threshold 4.55 cm2) and LA global mean voltage (GMV, threshold 1.66 mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination between AF types than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). In contrast, HATCH score and C2HEST score only achieved AUC < 0.60 in identifying individuals with persistent AF in current study.ConclusionAmong 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent, and mean LA voltage as the four determinant electrophysiological and structural factors that are most relevant for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF.

BackgroundContemporary data on atrial cardiomyopathy (ACM) markers and ischemic cerebrovascular events (ICVE) in patients with acute myocardial infarction (AMI) is lacking. We aimed to examine whether ACM markers predict ICVE among AMI patients.Materials and methodsA total of 4,206 AMI cases diagnosed in clinical examinations between January 2016 and June 2021 were assessed for markers of ACM including B-type natriuretic peptide (BNP), P-wave terminal force in ECG lead V1 (PTFV1), and left atrium diameter (LAD). Left atrial enlargement (LAE) and abnormal PTFV1 were defined by previously published cut-off points. The primary outcome was incident ICVE composed of ischemic stroke (IS) and transient ischemic attack (TIA). Receiver operating curve analyses were used to compare the predictive performance of the CHA2DS2-VASc score combined with ACM markers to the CHA2DS2-VASc score alone.ResultsDuring a median follow-up of 44.0 months, 229 (5.44%) ICVE occurred. Of these, 156 individuals developed IS and the remaining 73 cases were diagnosed with TIAs. The ICVE group showed larger PTFV1 and increased LAD as well as elevated BNP levels at baseline. In the multivariate analysis, we found significant associations with ICVE for PTFV1 (HR per 1,000 μV*ms, 1.143; 95% CI, 1.093–1.196), LAD (HR per millimeter, 1.148; 95% CI, 1.107–1.190), but not BNP after adjusting for known ICVE risk factors and interim atrial fibrillation (AF). The addition of abnormal PTFV1 and LAE improved the predictive accuracy of the CHA2DS2-VASc score with C-statistic increasing from 0.708 to 0.761 (p < 0.001).ConclusionAtrial cardiomyopathy markers including PTFV1 and LAD were associated with incident ICVE independent of well-established risk factors and AF occurrence. The addition of ACM markers with CHA2DS2-VASc score may well discriminate individuals at high risk of ICVE in AMI patients.

BackgroundReports of the clinical outcomes associated with the co-occurrence of atrial cardiomyopathy (ACM) and lung cancer (LC) are limited.ObjectivesThis study aims to investigate the influence of ACM on the prognosis of LC patients and related clinical determinants.MethodsNewly diagnosed LC patients from January 1st, 2015, to December 31st, 2020, were retrospectively enrolled at the First Affiliated Hospital of Xi’an Jiaotong University. The demographics and overall survival (OS) of the patients with or without ACM were compared. The survival rate was analyzed using the Kaplan–Meier method and multivariate Cox regression analysis. Binary logistic regression analysis was used to determine the risk factors for ACM.ResultsA total of 306 patients (65.04 ± 10.30 years of age, 72.88% male) were analyzed. The prevalence of ACM in the non-small cell lung cancer (241, 78.76%) and small cell lung cancer (65, 21.24%) population was not statistically different. Overall, 53 (17.32%) LC patients had coexisting ACM. ACM patients were older (69 vs. 64, p = 0.0013) and had higher D-dimer levels (1.0 vs. 0.6, p = 0.001), lower serum calcium levels (2.23 vs. 2.31, p = 0.001), lower left ventricular ejection fraction (LVEF) values (67% vs. 69%, p = 0.036) and had more frequent coronary comorbidity disease (16.98% vs. 8.82%, p = 0.031). The median OS for patients with or without ACM was 15 months and 25 months, respectively (p = 0.018). Coexisting ACM compared to non-ACM was associated with worse OS in patients with LC (HR = 1.543, 95% CI: 1.042–2.283, p = 0.030).ConclusionCoexisting ACM is associated with undesirable survival outcomes in patients with LC. These findings could help us to better understand the cardiac burden in these patients and provide additional risk stratification for them.

Left atrial cardiomyopathy (LACM) has been an ongoing focus of research for several years. There is evidence that LACM is responsible for atrial fibrillation and embolic strokes of undetermined sources. Therefore, the correct diagnosis of LACM is of clinical importance. Various techniques, including electrocardiography, echocardiography, cardiac magnetic resonance imaging, computed tomography, electroanatomic mapping, genetic testing, and biomarkers, can both identify and quantify structural, mechanical as well as electrical dysfunction in the atria. However, the question arises whether these techniques can reliably diagnose LACM. Because of its heterogeneity, clinical diagnosis is challenging. To date, there are no recommendations for standardized diagnosis of suspected LACM. However, standardization could help to classify LACM more precisely and derive therapeutic directions to improve individual patient management. In addition, uniform diagnostic criteria for LACM could be important for future studies. Combining several parameters and relating them seems beneficial to approach the diagnosis of LACM. This review provides an overview of the current evidence regarding the diagnosis of LACM, in which several potential parameters are discussed and, consequently, a proposal for a diagnostic algorithm is presented.

Background: Atrial 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., Methods: We 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., Results: Significant 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)., Conclusion: aFMR 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Mohsen, Rottländer, Großmann, Lewandowski, Horlitz and Stöckigt.)

Nearly 30% of ischemic strokes have an unknown cause, which are referred to as cryptogenic strokes (CS). Imaging studies suggest that a large proportion of these patients show features that are consistent with embolism, and thus the term embolic stroke of undetermined source (ESUS) was proposed to describe these CS patients. Atrial cardiomyopathy predisposes to thrombus formation and thus embolic stroke even in the absence of atrial fibrillation (AF). This may provide a mechanistic link with ESUS, suggesting that anticoagulant therapy may be more beneficial than antiplatelet therapy in ESUS patients with atrial cardiomyopathy. The present review discusses the concept of atrial cardiomyopathy and ESUS and the relationship between them based on the mechanisms and clinical evidence, suggests that atrial cardiomyopathy may be a potential mechanism of ESUS, and highlights a theoretical basis that supports that anticoagulant therapy may be more applicable to ESUS patients with atrial cardiomyopathy and aims to help us better understand and identify the risk of ESUS, thereby improving the management of these patients in clinical practice.

The most dreaded complication of atrial fibrillation is stroke, and 70–80% of patients with AF-related stroke die or become disabled. The mechanisms of thromboembolism in AF are multifactorial, with evidence demonstrating that all three criteria of Virchow's triad are satisfied in AF: abnormal stasis of blood, endothelial damage, and hypercoagulability. Mechanistic insights into the latter two limbs have resulted in effective stroke prophylactic therapies (left atrial appendage occlusion and oral anticoagulants); however, despite these advances, there remains an excess of stroke in the AF population that may be due, in part, to a lack of mechanistic understanding of atrial hypocontractility resulting in abnormal stasis of blood within the atrium. These observations support the emerging concept of atrial cardiomyopathy as a cause of stroke. In this Review, we evaluate molecular, translational, and clinical evidence for atrial cardiomyopathy as a cause for stroke from AF, and present a rationale for further investigation of this largely unaddressed limb of Virchow's triad in AF.

Introduction: Atrial 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., Methods: The 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 Discussion: Residence time was elevated in the AF group ( p  < 0.001). Linear regression analysis revealed that stasis was strongest associated with LA ejection ratio ( p  < 0.001, R 2  = 0.68) and the ratio of LA volume and left ventricular stroke volume ( p  < 0.001, R 2  = 0.81). Stroke risk due to LA thrombi could already be elevated in AF patients during sinus rhythm. In the future, patient specific CFD simulations may add to the assessment of this risk and support diagnosis and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bäck, Skoda, Lantz, Henriksson, Karlsson, Persson, Carlhäll and Ebbers.)

Objective: To 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 Results: A 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&#95;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., Conclusion: The 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ning, Han, Qiu, Hong, Xia, Liu and Liu.)

Background: The association of electrocardiographic (ECG) markers of atrial cardiomyopathy with heart failure (HF) and its subtypes is unclear., Methods: This 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., Results: 413 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., Conclusions: Atrial 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ahmad, Mujtaba, Floyd, Chen and Soliman.)

Changes in atrial size and function have historically been considered a surrogate marker of ventricular dysfunction. However, it is now recognized that atrial cardiomyopathy (ACM) may also occur as a primary myocardial disorder. Emerging evidence that ACM is a major risk factor for atrial fibrillation, heart failure, and thromboembolic stroke, has highlighted the significance of this disorder and the need for better assessment of atrial metrics in clinical practice. Key barriers in this regard include a lack of standardized criteria or hierarchy for the diagnosis of ACM and lack of consensus for the most accurate phenotyping methods. In this article we review existing literature on ACM, with a focus on current and future non-invasive imaging methods for detecting abnormalities of atrial structure and function. We discuss the relative advantages and disadvantages of transthoracic echocardiography and cardiac magnetic resonance imaging for assessing a range of parameters, including atrial size and contractile function, strain, tissue characteristics, and epicardial adipose tissue. We will also present the potential application of novel imaging methods such as sphericity index and four- or five-dimensional flow., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Kessler Iglesias, Pouliopoulos, Thomas, Hayward, Jabbour and Fatkin.)

Introduction: Outcomes of catheter ablation for non-paroxysmal atrial fibrillation (AF) remain suboptimal. Non-invasive stratification of patients based on the presence of atrial cardiomyopathy (ACM) could allow to identify the best responders to pulmonary vein isolation (PVI)., Methods: Observational multicentre retrospective study in patients undergoing cryoballoon-PVI for non-paroxysmal AF. The duration of amplified P-wave (APW) was measured from a digitally recorded 12-lead electrocardiogram during the procedure. If patients were in AF, direct-current cardioversion was performed to allow APW measurement in sinus rhythm. An APW cut-off of 150 ms was used to identify patients with significant ACM. We assessed freedom from arrhythmia recurrence at long-term follow-up in patients with APW ≥ 150 ms vs. APW < 150 ms., Results: We included 295 patients (mean age 62.3 ± 10.6), of whom 193 (65.4%) suffered from persistent AF and the remaining 102 (34.6%) from long-standing persistent AF. One-hundred-forty-two patients (50.2%) experienced arrhythmia recurrence during a mean follow-up of 793 ± 604 days. Patients with APW ≥ 150 ms had a significantly higher recurrence rate post ablation compared to those with APW < 150 ms (57.0% vs. 41.6%; log-rank p  < 0.001). On a multivariable Cox-regression analysis, APW≥150 ms was the only independent predictor of arrhythmia recurrence post ablation (HR 2.03 CI 95% 1.28-3.21; p  = 0.002)., Conclusion: APW duration predicts arrhythmia recurrence post cryoballoon-PVI in persistent and long-standing persistent AF. An APW cut-off of 150 ms allows to identify patients with significant ACM who have worse outcomes post PVI. Analysis of APW represents an easy, non-invasive and highly reproducible diagnostic tool which allows to identify patients who are the most likely to benefit from PVI-only approach., Competing Interests: SB is a consultant for Medtronic and Boston Scientific. AC has received an educational grant from Abbott and consultant fees from Boston Scientific. RJS has received research grants and speaker fees from Abbott, Medtronic, Boston Scientific, Johnson and Johnson and is a shareholder of AI Rhythm. MF has received research support from Abbott; Chief Medical Officer, Founder and Shareholder of Echopoint Medical Ltd; Director, Founder and Shareholder of Rhythm AI and Founder and Shareholder of Epicardio Ltd. RJH is founder and shareholder of Rhythm AI Ltd. PDL has received educational grants from Medtronic and Boston Scientific, and is supported by UCLH Biomedicine NIHR and Barts BRC funding. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Creta, Venier, Tampakis, Providencia, Sunny, Defaye, Earley, Finlay, Hunter, Lambiase, Papageorgiou, Schilling, Sporton, Andrikopoulos, Deschamps, Albenque, Cardin, Combes, Combes, Vinolas, Moreno-Weidmann, Huang, Eichenlaub, Müller-Edenborn, Arentz, Jadidi and Boveda.)

Aim: This study sought to develop and validate diagnostic models to identify individuals with atrial fibrillation (AF) using amplified sinus-p-wave analysis., Methods: A total of 1,492 patients (491 healthy controls, 499 with paroxysmal AF and 502 with persistent AF) underwent digital 12-lead-ECG recording during sinus rhythm. The patient cohort was divided into training and validation set in a 3:2 ratio. P-wave indices (PWI) including duration of standard p-wave (standard PWD; scale at 10 mm/mV, sweep speed at 25 mm/s) and amplified sinus-p-wave (APWD, scale at 60-120 mm/mV, sweep speed at 100 mm/s) and advanced inter-atrial block (aIAB) along with other clinical parameters were used to develop diagnostic models using logistic regression. Each model was developed from the training set and further tested in both training and validation sets for its diagnostic performance in identifying individuals with AF., Results: Compared to standard PWD (Reference model), which achieved an AUC of 0.637 and 0.632, for training and validation set, respectively, APWD (Basic model) importantly improved the accuracy to identify individuals with AF (AUC = 0.86 and 0.866). The PWI-based model combining APWD, aIAB and body surface area (BSA) further improved the diagnostic performance for AF (AUC = 0.892 and 0.885). The integrated model, which further combined left atrial diameter (LAD) with parameters of the PWI-based model, achieved optimal diagnostic performance (AUC = 0.916 and 0.902)., Conclusion: Analysis of amplified p-wave during sinus rhythm allows identification of individuals with atrial fibrillation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Schurr, Muller-Edenborn, Pilia, Mayer, Eichenlaub, Allgeier, Heidenreich, Ahlgrim, Bohnen, Lehrmann, Trenk, Neumann, Westermann, Arentz and Jadidi.)

Background: Progressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy (ACM) and the transition from paroxysmal to persistent atrial fibrillation (AF). We sought to identify the anatomical/structural and electrophysiological factors involved in atrial remodeling that promote AF persistency., Methods: Consecutive patients with paroxysmal ( n = 134) or persistent ( n = 136) AF who presented for their first AF ablation procedure were included. Patients underwent left atrial (LA) high-definition mapping (1,835 ± 421 sites/map) during sinus rhythm (SR) and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical mapping and non-invasive baseline data were extracted encompassing four main categories: (1) LA size, (2) extent of low-voltage-substrate (LVS), (3) LA voltages and (4) bi-atrial conduction time as identified by the duration of amplified P-wave (APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness. In addition, HATCH score and C2HEST score were also evaluated for their performance in identification of AF persistency., Results: In training and validation sets, APWD (threshold 151 ms), LA volume (LAV, threshold 94 mL), bipolar LVS area < 1.0 mV (threshold 4.55 cm 2 ) and LA global mean voltage (GMV, threshold 1.66 mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination between AF types than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). In contrast, HATCH score and C2HEST score only achieved AUC < 0.60 in identifying individuals with persistent AF in current study., Conclusion: Among 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent, and mean LA voltage as the four determinant electrophysiological and structural factors that are most relevant for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Nairn, Chen, Mueller-Edenborn, Pilia, Mayer, Eichenlaub, Moreno-Weidmann, Allgeier, Trenk, Ahlgrim, Westermann, Arentz, Loewe and Jadidi.)

Background: Contemporary data on atrial cardiomyopathy (ACM) markers and ischemic cerebrovascular events (ICVE) in patients with acute myocardial infarction (AMI) is lacking. We aimed to examine whether ACM markers predict ICVE among AMI patients., Materials and Methods: A total of 4,206 AMI cases diagnosed in clinical examinations between January 2016 and June 2021 were assessed for markers of ACM including B-type natriuretic peptide (BNP), P-wave terminal force in ECG lead V1 (PTFV1), and left atrium diameter (LAD). Left atrial enlargement (LAE) and abnormal PTFV1 were defined by previously published cut-off points. The primary outcome was incident ICVE composed of ischemic stroke (IS) and transient ischemic attack (TIA). Receiver operating curve analyses were used to compare the predictive performance of the CHA 2 DS 2 -VASc score combined with ACM markers to the CHA 2 DS 2 -VASc score alone., Results: During a median follow-up of 44.0 months, 229 (5.44%) ICVE occurred. Of these, 156 individuals developed IS and the remaining 73 cases were diagnosed with TIAs. The ICVE group showed larger PTFV1 and increased LAD as well as elevated BNP levels at baseline. In the multivariate analysis, we found significant associations with ICVE for PTFV1 (HR per 1,000 μV*ms, 1.143; 95% CI, 1.093-1.196), LAD (HR per millimeter, 1.148; 95% CI, 1.107-1.190), but not BNP after adjusting for known ICVE risk factors and interim atrial fibrillation (AF). The addition of abnormal PTFV1 and LAE improved the predictive accuracy of the CHA 2 DS 2 -VASc score with C-statistic increasing from 0.708 to 0.761 ( p < 0.001)., Conclusion: Atrial cardiomyopathy markers including PTFV1 and LAD were associated with incident ICVE independent of well-established risk factors and AF occurrence. The addition of ACM markers with CHA 2 DS 2 -VASc score may well discriminate individuals at high risk of ICVE in AMI patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Liu, Li, Gao, Yang, Wang, Hidru, Liu, Yang and Xia.)

Background: Reports of the clinical outcomes associated with the co-occurrence of atrial cardiomyopathy (ACM) and lung cancer (LC) are limited., Objectives: This study aims to investigate the influence of ACM on the prognosis of LC patients and related clinical determinants., Methods: Newly diagnosed LC patients from January 1st, 2015, to December 31st, 2020, were retrospectively enrolled at the First Affiliated Hospital of Xi'an Jiaotong University. The demographics and overall survival (OS) of the patients with or without ACM were compared. The survival rate was analyzed using the Kaplan-Meier method and multivariate Cox regression analysis. Binary logistic regression analysis was used to determine the risk factors for ACM., Results: A total of 306 patients (65.04 ± 10.30 years of age, 72.88% male) were analyzed. The prevalence of ACM in the non-small cell lung cancer (241, 78.76%) and small cell lung cancer (65, 21.24%) population was not statistically different. Overall, 53 (17.32%) LC patients had coexisting ACM. ACM patients were older (69 vs. 64, p = 0.0013) and had higher D-dimer levels (1.0 vs. 0.6, p = 0.001), lower serum calcium levels (2.23 vs. 2.31, p = 0.001), lower left ventricular ejection fraction (LVEF) values (67% vs. 69%, p = 0.036) and had more frequent coronary comorbidity disease (16.98% vs. 8.82%, p = 0.031). The median OS for patients with or without ACM was 15 months and 25 months, respectively ( p = 0.018). Coexisting ACM compared to non-ACM was associated with worse OS in patients with LC (HR = 1.543, 95% CI: 1.042-2.283, p = 0.030)., Conclusion: Coexisting ACM is associated with undesirable survival outcomes in patients with LC. These findings could help us to better understand the cardiac burden in these patients and provide additional risk stratification for them., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Ma, Wei, Ning, Liu, Shi, Yao and Guo.)

Left atrial cardiomyopathy (LACM) has been an ongoing focus of research for several years. There is evidence that LACM is responsible for atrial fibrillation and embolic strokes of undetermined sources. Therefore, the correct diagnosis of LACM is of clinical importance. Various techniques, including electrocardiography, echocardiography, cardiac magnetic resonance imaging, computed tomography, electroanatomic mapping, genetic testing, and biomarkers, can both identify and quantify structural, mechanical as well as electrical dysfunction in the atria. However, the question arises whether these techniques can reliably diagnose LACM. Because of its heterogeneity, clinical diagnosis is challenging. To date, there are no recommendations for standardized diagnosis of suspected LACM. However, standardization could help to classify LACM more precisely and derive therapeutic directions to improve individual patient management. In addition, uniform diagnostic criteria for LACM could be important for future studies. Combining several parameters and relating them seems beneficial to approach the diagnosis of LACM. This review provides an overview of the current evidence regarding the diagnosis of LACM, in which several potential parameters are discussed and, consequently, a proposal for a diagnostic algorithm is presented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kreimer and Gotzmann.)

Nearly 30% of ischemic strokes have an unknown cause, which are referred to as cryptogenic strokes (CS). Imaging studies suggest that a large proportion of these patients show features that are consistent with embolism, and thus the term embolic stroke of undetermined source (ESUS) was proposed to describe these CS patients. Atrial cardiomyopathy predisposes to thrombus formation and thus embolic stroke even in the absence of atrial fibrillation (AF). This may provide a mechanistic link with ESUS, suggesting that anticoagulant therapy may be more beneficial than antiplatelet therapy in ESUS patients with atrial cardiomyopathy. The present review discusses the concept of atrial cardiomyopathy and ESUS and the relationship between them based on the mechanisms and clinical evidence, suggests that atrial cardiomyopathy may be a potential mechanism of ESUS, and highlights a theoretical basis that supports that anticoagulant therapy may be more applicable to ESUS patients with atrial cardiomyopathy and aims to help us better understand and identify the risk of ESUS, thereby improving the management of these patients in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ning, Tse, Luo and Li.)

Atrial Fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF is difficult to treat and therefore there is a great need to dissect root causes of AF with the ultimate goal to develop mechanism-based (drug) therapies. New findings related to mechanisms driving AF progression indicate a prime role for DNA damage-induced metabolic remodeling. A recent study uncovered that AF results in oxidative DNA damage and consequently excessive poly-ADP-ribose polymerase 1 (PARP1) activation and nicotinamide adenine dinucleotide (NAD + ) depletion and finally atrial cardiomyocyte electrical and contractile dysfunction. This newly elucidated role of DNA damage in AF opens opportunities for novel therapeutic strategies. Recently developed PARP inhibitors, such as ABT-888 and olaparib, provide beneficial effects in limiting experimental AF, and are also found to limit atherosclerotic coronary artery disease and heart failure. Another therapeutic option to protect against AF is to replenish the NAD + pool by supplementation with NAD + or its precursors, such as nicotinamide and nicotinamide riboside. In this review, we describe the role of DNA damage-mediated metabolic remodeling in AF and other cardiovascular diseases, discuss novel druggable targets for AF and highlight future directions for clinical trials with drugs directed at PARP1-NAD + pathway with the ultimate aim to preserve quality of life and to attenuate severe complications such as heart failure or stroke in patients with AF., (Copyright © 2020 Ramos and Brundel.)

The most dreaded complication of atrial fibrillation is stroke, and 70-80% of patients with AF-related stroke die or become disabled. The mechanisms of thromboembolism in AF are multifactorial, with evidence demonstrating that all three criteria of Virchow's triad are satisfied in AF: abnormal stasis of blood, endothelial damage, and hypercoagulability. Mechanistic insights into the latter two limbs have resulted in effective stroke prophylactic therapies (left atrial appendage occlusion and oral anticoagulants); however, despite these advances, there remains an excess of stroke in the AF population that may be due, in part, to a lack of mechanistic understanding of atrial hypocontractility resulting in abnormal stasis of blood within the atrium. These observations support the emerging concept of atrial cardiomyopathy as a cause of stroke. In this Review, we evaluate molecular, translational, and clinical evidence for atrial cardiomyopathy as a cause for stroke from AF, and present a rationale for further investigation of this largely unaddressed limb of Virchow's triad in AF., (Copyright © 2020 Darlington and McCauley.)