Atrial Cardiomyopathy Research Articles

Diabetic atrial cardiomyopathy can be identified by multiparametric mri MRI associating atrio-ventricular groove adipose tissue and left atrial strain profiles

Abstract Background Epicardial adipose tissue (EAT) is tightly associated with neighboring myocardium with free diffusion between the two tissues of fatty acid, peptides and adipokines. In specific circumstances EAT can favors myocardial remodeling and, for instance, contribute to the risk of atrial fibrillation (AF). Thereby, there is a growing interest for EAT as a biomarker of AF however, which is limited by difficulties of delineation of EAT vs. other paracardial adipose tissues. The atrio-ventricular groove adipose tissue (GEAT) has been proven to be pure epicardial adipose tissue. Purpose We tested the feasibility and value of measuring pure EAT of the atrio-ventricular groove (GEAT) using routine cardiovascular magnetic resonance imaging (CMR) in a cohort of patients with distinct metabolic disorders and studied its correlates to determine a CMR cardiometabolic score. Methods One hundred patients from the METACARDIS cohort (EU FP7) who had MRI, all in sinus rhythm and without overt clinical heart disease, were divided into 4 groups based on distinct metabolic profiles: metabolic syndrome (MSD, n=25), severe obesity (SO, BMI ≥ 35 kg/m2, n=18), type-2 diabetes (T2D, n=42) and healthy controls (n=15). Atrioventricular groove EAT volume was measured from cine SSFP MRI images in four-, three-, two-chamber and short-axis views; atrial EAT volume was measured from four- and two-chamber views. Native T1-mapping values of EAT at the anterior atrioventricular groove excluding the coronary vessels were measured from the MOLLI sequence (basal short-axis slice). Results CMR was performed in 100 patients from the MetaCardis cohort. GEAT volume measured from end-diastolic long axis views was obtained in all patients with a high correlation between GEAT and atrial EAT (r=0.95; P<0.0001). GEAT volume was higher in the 3 groups of patients with metabolic disorders and highest in MSD. Together with age, body mass, fat distribution, GEAT volume allowed to distinguish obese, T2D and MSD from controls. T2D patients were uniquely characterized in CMR by decreased GEAT T1 relaxation and decreased peak longitudinal left atrial strain. We developed a CMR score by logistic regression and Random Forest machine-learning algorithm combining GEAT volume, T1 and peak LA strain that identified T2D patients with an AUC of 0.81 (Se:77%, Spe:80%; 95%-CI 0.72–0.91, p <0.0001). Conclusion The epicardial adipose tissue of the AV groove measured by CMR can be used as the proxy of atrial EAT and, in combination with atrial strain and T1 relaxation, allows the early identification of the atrial cardiomyopathy associated with diabetes. There is diagnostic value of a multiparametric CMR approach for the detection of subclinical atrial cardiomyopathy and potentially to identify patients at risk of atrial fibrillation and stroke.

Dissociation of LA volume and deformation is a hallmark of ATTR-CA

Abstract Background Transthyretin Cardiac amyloidosis (ATTR-CA) is associated with an infiltrative left atrial (LA) cardiomyopathy. Purpose We sought to identify unique characteristics of LA cardiomyopathy in CA compared to non-amyloid states of left ventricular hypertrophy (LVH). Methods In suspected patients, a diagnosis of ATTR-CA was made by a positive Tc-99m PYP in conjunction with negative serum/urine studies for a clonal plasma cell dyscrasia. Endomyocardial biopsy was performed when clinically indicated. All patients underwent complete transthoracic echocardiography (TTE) with speckle tracking strain imaging. Left ventricular (LV) strain, LA reservoir strain (LASr) and LA volume index (LAVI) were measured. LA stiffness index was estimated by the ratio (E/e’)/LASr. ATTR-CA patients were compared to patient with non- CA LVH (interventricular septal thickness > 1.2 cm). Atrial fibrillation (AF) during the TTE was noted. Logistic regression and Cox-regression analyses were performed to find the independent determinant of ATTR-CA and outcome predictors, respectively. Results We studied 98 patients with ATTR-CA (44 with AF) and 62 patients with non-CA LVH (35 with AF). ATTR-CA patients had a higher prevalence of relative apical sparing (RAS) (79% vs 20%, p<0.0001), reduced LASr (9.8±4.8% vs 14.0±7.2%; p<0.001) and high LA stiffness (2.5±0.2 vs 1.4±0.9; p<0.001) irrespective of AF. Surprisingly, LAVI of ATTR-CA patients was significantly lower than non- CA LVH patients (44±15 ml/m2 vs 51±24 ml/m2; p=0.046). Consequently, LAVI correlated strongly with LASr in non-amyloid LVH group (r= -0.52, p<0.001) whereas no correlation was observed in ATTR-CA (p<0.05) (Figure 1). Patients with ATTR-CA had the lowest LASr and highest LA stiffness regardless of AF (Figure 2). Importantly, LASr determined ATTR-CA among all study subjects independently of RAS (p<0.001) and emerged as a predictor of composite endpoint including all-cause mortality, hospitalization from heart failure and stroke in ATTR-CA patients (p=0.037). Conclusion ATTR-CA is characterized by severely reduced LASr and increased LA stiffness, yet LA dilatation is relatively less severe when compared to other causes of LVH. LASr seems promising to make the differential diagnosis of ATTR-CA and is of prognostic importance.Figure 1Figure 2

Right atrial strain predicts collagen mRNA levels in human right atrium

Abstract Background Structural remodelling, which includes increased fibrosis and collagen production, is a hallmark of atrial cardiomyopathy. Echocardiographic strain measurements allow detailed assessment of atrial function. We investigated the association between right atrial (RA) strain and collagen mRNA levels in human RA. Methods RA biopsies were collected from 21 patients undergoing elective coronary artery bypass grafting in the prospective observational study CONSIDER-AF. Tissue mRNA levels of collagen type I (Col1A) and of collagen type III (Col3A) were quantified using real-time qPCR on ViiA 7 real-time PCR system. Echocardiographic RA strain (reservoir, conduit, and booster function) was measured in the four-chamber view using the designated software Philips QLAB. We performed uni- and multivariable linear regression analysis to elucidate the relationship between RA strain and collagen mRNA levels. Results There was a strong correlation between RA reservoir strain and Col1A mRNA levels (p=0.0152, r²=0.2608, Fig A) and Col3A mRNA levels (p=0.0058, r²=0.3374, Fig B) as well as between RA conduit strain and Col1A mRNA levels (p=0.0301, r²=0.2141, Fig C) and Col3A mRNA levels (p=0.0232, r²=0.2430, Fig D). However, there was no correlation between RA booster function and Col1A levels (p=0.5572, Fig E) or Col3A levels (p=0.3426, Fig F). Multivariate regression analysis revealed that RA conduit and RA reservoir function are predictors for Col1A and Col3A mRNA levels independent from clinical covariates (age, sex, body-mass index, systolic blood pressure). Discussion Our findings show that RA strain measurements are associated with RA collagen mRNA levels in humans and therefore highlight the potential of strain analysis to identify structural remodelling in atrial cardiomyopathy.FigureTable

Role of atrial lymphatics in atrial myocardial fibrosis and atrial fibrillation: a human and mouse study

Abstract Background/Introduction Cardiac lymphatics maintain myocardial fluid and immune cell homeostasis, but its effects on atrial fibrosis and atrial fibrillation (AF) have not been clarified. Purpose To address this issue, we first evaluated the left atrial appendage (LAA) in humans histologically and biologically. We then studied mice to elucidate the mechanisms. Methods Human LAA samples were collected from 34 consecutive AF patients during cardiovascular surgery. They were assigned to the paroxysmal AF (PAF) group (n=17, 70.9±11.6 years) and the persistent AF (PeAF) group (n=17, 72.1±7.2 years). In the mouse experiments, 8-week-old male C57BL/6 mice were administrated subcutaneously with vehicle or Angiotensin II (AngII) (2.0 mg/kg/day) for 4 weeks. In some mice, VEGFC, a pro-lymphangiogenesis inducer, was administrated subcutaneously at a dose of 50 μg/kg/day simultaneously with AngII. AF was induced by transesophageal burst pacing in vivo, and by burst pacing in isolated perfused hearts using a Langendorff apparatus. Results In human LAA samples, mRNA expression of lymphangiogenesis-related genes (LYVE1, PROX1, and VEGFR3) was significantly lower in the PeAF group compared to the PAF group (p=0.037, 0.029, and 0.041). The number of LYVE1-positive atrial lymphatic endothelial cells (LECs) was also significantly lower in the PeAF group compared to the PAF group (p=0.026). There was a negative correlation between the number of LYVE1-positive atrial LECs and the area percentage of atrial myocardial fibrosis (r=-0.609, p<0.001). In mouse experiments, continuous infusion of AngII suppressed the mRNA expression of lymphangiogenesis-related genes, including Lyve1, Prox1, and Vegfr3 (n=6 in each group, p<0.001, p=0.003, and p<0.001, respectively). AngII infusion reduced the number of LYVE1-positive atrial LECs (p<0.001) and increased the mRNA expression of fibrosis-related genes (Tgfb, Col1a1, and Col3a1). The area percentage of fibrosis in atrial myocardium was also increased by AngII. Treatment with VEGFC for 4 weeks effectively reversed the effects of AngII, i.e., suppression of lymphangiogenesis-related genes expression, reduction of LYVE1-positive atrial LECs, increase in fibrosis-related genes expression, and increase in atrial fibrosis. Additionally, VEGFC treatment attenuated AngII-induced enhancement of vulnerability to AF in in vivo experiments (n=8 in each group, p=0.007) and in isolated perfused hearts (n=8 in each group, p=0.007). Conclusions Our study with human LAA demonstrated a strong association between atrial lymphatics and atrial myocardial fibrosis/progression of AF. Our mouse study showed that VEGFC reversed AngII -induced increase in atrial myocardial fibrosis and vulnerability to AF, possibly via promotion of lymphangiogenesis. Defects of lymphangiogenesis may be involved in atrial myocardial fibrosis and AF, and may be a therapeutic target for atrial cardiomyopathy.

Pulsed field ablation for atrial fibrillation - Lessons from magnetic resonance imaging.

Pulsed field ablation (PFA) is a promising technology for the treatment of atrial fibrillation (AF). Due to its unique tissue selectivity, PFA potentially bears superior characteristics as compared to established thermal energy sources in AF ablation procedures. Cardiovascular magnetic resonance imaging (CMR) using late gadolinium enhancement (LGE) is an established tool in the analysis of myocardial fibrosis representing atrial cardiomyopathy as well as ablation-induced atrial scar formation following catheter ablation with thermal energy. Mechanisms of atrial lesion formation differ between thermal ablation and electroporation and its impact on results of CMR imaging are not fully understood until now. In this review article, the potential of CMR imaging for PFA lesion assessment and available data are discussed. Further, additional needs to adopt imaging approaches to the cellular mechanisms of electroporation are considered.

Abstract 16625: Frameshift Mutation in LMNA Gene Causes Atrial Arrhythmogenesis via Epigenetic Inhibition of KCNA5 Expression

Introduction: Cardiolaminopathy is a genetic heart disease caused by LMNA mutations, often leading to atrial tachycardia, AV block, ventricular arrhythmia and eventually dilated cardiomyopathy. While performing WES on pedigrees with primary atrial myopathy, we identified that nearly half of them possess mutations on the LMNA gene. However, previous studies on laminopathy have mainly focused on ventricular lesions, leaving the mechanism of how LMNA mutation leads to the atrial myopathy yet to be elucidated. Methods: To better understand the role of the LMNA gene in atrial cardiomyopathy, we employed the CRISPR/Cas9 to establish a heterozygous KI mouse model with a frameshift mutation ( lmna c.1249delA, p.K418Sfs) identified from a pedigree of atrial cardiomyopathy. Results: The heterozygous mice displayed progressive and spontaneous atrial arrhythmia, along with increased fibrosis, without any involvement of the ventricles, which was consistent with the affected individuals in the pedigree. Electrophysiological measurements showed prolonged APD90, an increased occurrence of EAD events, and augmented atrial conduction heterogeneity compared to the control mice. Bioinformatics analysis of mouse atrium indicated KCNA5 , which specifically expressed in the atrium, was significantly down-regulated. This reduction was further corroborated through Western blotting and immunofluorescence. Additionally, ChIP qPCR analysis revealed an enhanced binding of KCNA5 with lamin A/C and reduced binding with the promoting histone H3K4me3 in the mutant atrium. Notably, the presence of atrial arrhythmia and the downregulation of KCNA5 were also observed in another lmna frameshift mutation mouse model, suggesting that these mechanisms may be universal in LMNA -related atrial cardiomyopathy. Conclusions: Laminopathy causing atrial cardiomyopathy has long been underestimated. Our study validates the pathogenicity of LMNA frameshift mutation for the atrium and highlights epigenetic changes leading to KCNA5 expression downregulation and consequential phenotypic alterations. These results broaden the current knowledge of laminopathy beyond its previous emphasis on ventricular lesions, offering potential therapeutic targets for the disease.

Abstract 13327: Mechanistic Basis of Sinoatrial Node Pacemaker Failure in Atrial Cardiomyopathy

Introduction: Sinoatrial node (SAN) dysfunction commonly occurs in atrial cardiomyopathy (ACM: “tachy-brady syndrome”), often requiring pacemaker implantation, but mechanisms are unknown. Atrial-selective myosin light chain-4 (MYL-4) mutations cause familial ACM with a high rate of early SAN dysfunction and pacemaker requirement. We studied rats engineered with a knock-in MYL-4 clinical E11K mutation and addressed mechanisms of SAN dysfunction. Methods: Atrial electrical properties were assessed with in vivo electrophysiology (EPS), ex vivo optical mapping, SAN single-cell voltage and current clamp, Ca 2+ -handling with Ca 2+ -sensitive dye microscopy. Gene expression was assessed by qPCR and fibrosis with Masson-Trichrome stain. Results: E11K rats showed progressive SAN recovery-time increases (Fig. A) and conduction-slowing (Fig. B). SAN cells showed slowed phase-4 depolarization (Fig. C) and reduced pacemaker “funny” current (I f ) (Fig. D). Ca 2+ homeostasis was also affected, showing decreased Ca 2+ -transients (Fig. E). SAN also displayed remodeling with increased collagen deposition (Fig. F). Conclusions: ACM resulting from E11K mutation induces multimodal electrical and structural remodeling of the SAN region, worsening with age. These observations provide new insights into mechanisms of the clinically important tachy-brady syndrome associated with ACM.

Abstract 14299: Low Left Atrial Motion Automatically Calculated is Indicator of Atrial Cardiomyopathy and High Risk of Cardioembolic Stroke

Background: Atrial cardiomyopathy is considered to be an important risk factor for cardioembolic stroke. However, little is known how to evaluate the degree of atrial cardiomyopathy. Hypothesis: Left atrial ejection fractions (LAEF) are useful and more sensitive predictors of cardioembolic stroke. Aim; To identify the relationship between LAEF and clinical events such as cardioembolic stroke. Methods: The left atrial appendage closure (LAAC) database of our institution from February 2020 to April 2023 was retrospectively analyzed. The LAEF was calculated from cardiovascular computed tomography (CT) imaging data using the automatic 3-dimensional chamber analysis software. We examined the relationship between the risk of cardioembolic stroke and LAEF. Results: We enrolled 52 consecutive patients who underwent cardiovascular CT before LAAC (age, 75.3±1.1 years; female gender, 26.9%; BMI, 23.3±0.5 kg/m 2 ; CHA 2 DS 2 -VASc score, 4.8±0.2; HAS-BLED score, 3.3±0.1). Of those, 22 (42.3%) patients had histories of cardioembolic stroke. Comparison between patients with and without cardioembolic stroke were shown in Table1. Receiver-operating characteristic curve analysis confirmed that 16.32% was the best cut-off value of LAEF for the history of cardioembolic stroke (AUC = 0.81). In the multivariate analysis, LAEF ≤ 16.32% is the independent predictor for cardioembolic stroke (p-value = 0.0362, respectively) (Table2). Conclusions: Low left atrial motion was potential risk factor for cardioembolic stroke in this population. This result could have a relevant impact on the antithrombotic management of patients and, moreover, LAAC could be the best option for these patients.

Abstract 16636: Correlation Between Interatrial Block Detected by High-Resolution Electrocardiography and Echocardiographic Markers of Left Atrial Cardiomyopathy

Introduction: Left atrial cardiomyopathy (LACM) involves electromechanical changes in the left atrium (LA) and is linked to atrial fibrillation (AF) and embolic stroke. Several diagnostic ECG and transthoracic echocardiogram (TTE) parameters have been suggested, but information about their interrelationship is limited. Hypothesis: To evaluate if partial or advanced interatrial block (IAB) using high-resolution 12-lead ECG (HR-ECG) is related to TTE indicators of LACM. Methods: A retrospective analysis of consecutive patients aged over 18 was performed. The evaluation included HR-ECG (signal-averaging technique, ≥ 200 cycles, QRS-triggered, 0.25-262 Hz bandwidth, 1000 samples/sec) and TTE. Exclusion criteria: AF, pacemaker/ICD carriers, heart surgery history, poor ultrasound window, or significant ECG noise. Inferior leads (DII, DIII, aVF) classified patients into three groups: no IAB, partial IAB (P wave ≥ 120 ms), and advanced IAB (typical/atypical patterns with negative aVF terminal component). TTE parameters of LACM considered were LA volume indexed to body surface area (LAVI), PA-TDI (surface ECG onset P wave to A' peak of LA lateral wall on Tissue-Doppler Imaging), and PALS (peak atrial longitudinal strain) during reservoir phase. Results: Of 851 patients, 533 met the inclusion criteria. Both IAB groups had a higher prevalence of TTE indicators of LACM (Table 1), and a statistically significant correlation was found between P wave duration (PWD) and TTE markers of LACM (Figure 1). Conclusions: Patients with partial or advanced IAB (assessed by HR-ECG) show a higher prevalence of TTE markers of LACM and a significant correlation between PWD, LAVI, PA-TDI, and PALS.

Impact of enzyme replacement therapy and migalastat on left atrial strain and cardiomyopathy in patients with Fabry disease.

Cardiomyopathy in Fabry disease (FD) is a major determinant of morbidity and mortality. This study investigates the effects of FD-specific treatment using enzyme replacement therapy (ERT) and chaperone therapy on left atrial (LA) function using two-dimensional speckle tracking echocardiography (2DSTE). In this prospective observational single-center study, 20 FD patients [10 (50%) females] treated with migalastat, 48 FD patients [24 (50%) females] treated with ERT (agalsidase-alfa and agalsidase-beta), and 30 untreated FD patients (all females) as controls were analyzed. The mean follow-up time ranged from 26 to 81 months. 2DSTE was performed for left ventricle strain, right ventricle strain, and LA strain (LAS). FD-specific treated patients presented with increased left ventricular mass index (LVMi) and higher frequency of left ventricular hypertrophy at baseline, whereas untreated control patients showed normal baseline values. FD-specific treated (including migalastat and ERT) patients showed stabilization of LAS over time (p > 0.05). LVMi was also stable in treated FD patients during observation (p > 0.05). In patients with FD, treated with either ERT or chaperone therapy, LAS values measured by echocardiographic speckle tracking were stable over time, pointing toward disease stabilization.

Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis

SummaryTwo siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)–converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions

Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.

Predictive value of P wave parameters, indices, and a novel electrocardiographic marker for silent cerebral infarction and future cerebrovascular events

BackgroundSilent cerebral infarction (SCI) is a neuronal injury without a clinically apparent stroke or transient ischaemic attack. Left atrial cardiomyopathy is closely associated with SCI. P wave changes in the electrocardiogram (ECG) provide significant information about the development of atrial cardiomyopathy. This study evaluated the role of P wave parameters and indices and a novel ECG parameter in predicting SCI, future cerebrovascular events, and atrial fibrillation/flutter. Materials and methodsA total of 272 patients were retrospectively screened and divided into two groups according to SCI. Cerebrovascular events and atrial fibrillation/flutter were defined as the study's outcomes. P wave parameters, indices, and a novel ECG parameter called the P wave ratio (PWR) were calculated from ECGs, and the relationship between SCI and outcomes was investigated. ResultsThe maximum P wave duration (PWD), P wave dispersion (PWdisp), PWD measured from the D2 lead (PWDD2), P wave peak time measured from the D2 lead (PWPTD2), PWPT measured from the V1 lead (PWPTV1), and P wave terminal force (PWTFV1) were significantly longer in the SCI group. Both partial and advanced inter atrial block (IAB) were significantly high in the SCI group. The novel parameter P wave ratio (PWR) was significantly longer in the SCI group (0.55 ± 0.08 vs. 0.46 ± 0.09; p < 0.001). In multivariate regression analysis, PWdisp (OR: 1.101, p < 0.001), PWPTD2 (OR: 1.095, p = 0.017), and PWR (OR: 1.231, p < 0.001) were found to be independent predictors of SCI. Cox regression analysis revealed that the PWR (HR 1.077; 95% CI 1.029–1.128; p = 0.001) was associated with cerebrovascular events and atrial fibrillation/flutter. ConclusionIn our study, we observed that PWR could be a valuable parameter for predicting SCI and future cerebrovascular events.

Study of mitral valve remodling in patients with atrial functional mitral valve regurgitation using three-dimensional echocardiography

Abstract Background The global burden of atrial fibrillation (AF) is enormous for healthcare systems. AF is typically classified into five distinct patterns depending on the onset, progression, and resolution of AF episodes, first diagnosed AF, paroxysmal AF, persistent AF, long-standing persistent AF&amp; permanent AF. Atrial structural remodeling or exacerbation of atrial cardiomyopathy are generally defining features of the transition from paroxysmal to non-paroxysmal AF. The duration of rhythm monitoring and the presence of a substrate are both important factors in determining the rate of AF development. In the existence of a structurally normal valve, functional MR develops when there is a mismatch between the tethering forces exerted by the heart &amp; the closing forces exerted by the heart. In the context of functional MR annular dilation alone, can constitute a separate etiology of MR (atrial functional MR). TEE provides supplementary imaging, particularly if TTE windows are technically challenging, making it a useful tool even if TTE is the primary technique for assessing and quantifying mitral valve disease. 3DE data sets can be acquired from either TTE or TEE approach, allowing real-time visualization of the cardiac structures, it is superior to 2DE in quantification of cardiac chamber volumes and function, assessment of the mechanisms and severity of heart valve diseases, evaluation of cardiac complex anatomy. Aim of the work To study mitral valve apparatus remodeling in patients with atrial functional mitral valve regurgitation using three-dimensional echocardiography. Methods This study included a total of 30 patients with diagnosis of atrial fibrillation divided in to two groups, 15 patients having no/ mild mitral regurgitation while 15 patients having moderate/severe mitral regurgitation, they were subjected to 2D and 3D TEE echocardiographic assessment of MR degree, LA volumes, mitral leaflets and mitral annulus parameters. Results There was statistically significant difference between the two groups as regard the posterior leaflet area as larger area was estimated in (Mod/severe MR) group compared to (No/ mild MR) group, with mean posterior leaflet area in group I was (8.96 ± 2.60) and (7.30 ± 2.17) in group II with (P value = 0.029) as well as there was statistically significant difference between the two groups as regard total leaflet area/Mitral annular area ratio as smaller ratio was estimated in (Mod/severe MR) group as compared to (No/mild MR) group, with the mean total leaflet area /mitral annular area ratio in group I was (1.22 ± 0.04) and (1.26 ± 0.04) in group II with (P value = 0.008). Conclusion Isolated annular dilatation can cause significant functional atrial mitral regurgitation while mitral leaflet area increases in AF as the annulus dilates, but this adaptation may plateau at larger annular areas, with the resulting leaflet deficiency causing functional atrial mitral regurgitation. Additional Content An author video to accompany this abstract is available on https://academic.oup.com/eurheartjsupp. Please click on the arrow next to ‘More Content’ and then click on ‘Author videos’.

Atrial fibrillation in patients with chronic kidney disease: features of pathogenesis and treatment

Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia in adults, the frequency of which increases in patients with chronic kidney disease (CKD). The substrate for the development of AF is atrial cardiomyopathy, which includes structural, electrophysiological and molecular remodeling of the atria. AF, in turn, can initiate and accelerate the progression of CKD. Such a bidirectional relationship causes a frequent combination of these two conditions, leading to both a prothrombotic state and an increased risk of bleeding. In patients with CKD, the pharmacokinetics of drugs used in AF are changing, what limits their use in CKD S4/S5. If previously patients with CKD S4-5 were excluded from randomized clinical trials (RCTs) on treatment strategies for AF, a number of such studies on their management have been published to date. The purpose of the article is to review existing ideas about the features of the pathogenesis of AF in CKD and strategies of recent years for the treatment of AF with advanced stages of CKD.

Optimizing fibrosis detection: a comparison of electroanatomical mapping and late enhancement gadolinium magnetic resonance imaging.

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. 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. 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. 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.

Atrial Abnormalities in Brugada Syndrome: Evaluation With ECG Imaging

BackgroundPatients with Brugada syndrome (BrS) have an increased risk of arrhythmias, including atrial tachyarrhythmias (ATas). ObjectivesThe purpose of this study was to assess underlying atrial cardiomyopathy in BrS and the effect of ajmaline (AJM) test on the atrium of BrS patients using electrocardiogram imaging (ECGI). MethodsAll consecutive patients diagnosed with BrS in a monocentric registry were screened and included if they met the following criteria: 1) BrS diagnosed following current recommendations; and 2) ECGI map performed before and after AJM with a standard protocol. Consecutive patients with no structural heart disease or BrS who had undergone ECGI were included as a control group. Genetic analysis for SCN5A was performed in all BrS patients. Total atrial conduction time (TACT) and local atrial conduction time (LACT) were calculated from atrial ECGI. The primary endpoint was ATas during follow-up. ResultsForty-three consecutive BrS patients and 40 control patients were included. Both TACT and LACT were significantly prolonged in BrS patients compared with control patients. Furthermore, TACT and LACT were significantly higher after AJM administration and in BrS patients who were carriers of a pathogenic/likely pathogenic SCN5A variant. After a mean follow-up of 40.9 months, 6 patients experienced a first ATa occurrence (all in the BrS group, 13.9%). TACT was the only independent predictor of ATas with a cutoff of >138.5 ms (sensitivity 0.92 [95% CI: 0.83-0.98], specificity 0.70 [95% CI: 0.59-0.81]). ConclusionsECGI-calculated TACT and LACT are significantly prolonged in BrS patients compared with control patients, and in BrS patients after AJM. This may be consistent with a concealed atrial cardiomyopathy in BrS.

Differences in atrial substrate localization using late gadolinium enhancement-magnetic resonance imaging, electrogram voltage, and conduction velocity: a cohort study using a consistent anatomical reference frame in patients with persistent atrial fibrillation.

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). 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 (R2 = 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). 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.

Magnetic resonance detection of advanced atrial cardiomyopathy increases the risk for atypical atrial flutter occurrence following atrial fibrillation ablation.

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. 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). 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.

Heart failure with improved ejection fraction in patients with tachycardia-induced cardiomyopathy: a case report

Heart failure and arrhythmias are pathogenetically closely interconnected and they are mutually aggravating each other. At the same time, tachycardia-induced cardiomyopathy is particularly a reversible disease with proper treatment. This article presents a case report of an elderly patient with hypertension and atrial fibrillation, which are associated to an advanced heart failure and complicating the management of a decreasing kidneys filtration capacity, hematuria and brain stroke. In this case report, tachycardia-induced cardiomyopathy is caused by persistent atrial fibrillation. A complex approach to diagnosis and evidence-based treatment (in particular cardioversion and radiofrequency ablation) made it possible to restore sinus rhythm and compensate heart failure. Dynamics of the clinical state of the patient, laboratory indicators, echocardiographic characteristics allowed us to retrospectively verify atrial fibrillation-mediated cardiomyopathy as the main cause of heart failure progression, and classify this clinical case as heart failure with improved ejection fraction.