Atrial Remodeling In Patients Research Articles

The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients’ exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO2, mean SpO2, and LA size (all p < 0.05) but not between the apnea–hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all p < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all p < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all p < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO2 and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO2 and HIF-1α (all p < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.

Predictors of Atrial Remodeling in Patients with Sleep Apnea: Analysis of Electrocardiographic and Echocardiographic Variables

Predictors of Atrial Remodeling in Patients with Sleep Apnea: Analysis of Electrocardiographic and Echocardiographic Variables

Spironolactone and Atrial Remodelling in Patients With Paroxysmal Atrial Fibrillation (PAF)

Spironolactone and Atrial Remodelling in Patients With Paroxysmal Atrial Fibrillation (PAF)

Molecular mechanism of atrial remodeling in patients with aging atrial fibrillation under the expression of microRNA-1 and microRNA-21

ABSTRACT We investigated the expression levels of microRNA-1 (miRNA-1) and microRNA-21 (miRNA-21) in the atrial tissues of patients with atrial fibrillation (AF) and the molecular mechanism of action in atrial remodeling. Patients with valvular heart disease were selected as the subjects. The ultrastructure, degree of myocardial fibrosis, apoptosis index (AI), expression of microRNA-1, expression of microRNA-21, and mRNA of TIMP-1, MMP-9, BCL-2, and Bax of patients were compared and analyzed in each group. The results showed that the degree of myocardial fibrosis and AI in patients with AF of the same age were extremely higher than those of patients with sinus rhythm (SR) (P < 0.01). Patients with AF showed much higher messenger RNA (mRNA) levels of mini-mental Parkinson 9 (MMP9) and Bax and obvious lover mRNA levels of tissue inhibitors of metalloproteinase 1 (TIMP-1) and Bcl-2 compared with patients with sinus rhythm (SR) (P < 0.05). It indicated that the expression of miRNA-1 in the AF patients was markedly down-regulated, and that miRNA-21 was up-regulated. This showed that microRNA-1 and microRNA-21 were involved in the molecular remodeling of aging AF through the regulation of primers, which would provide a critical basis for diagnosis and treatment of aging AF.

Macrophage Inflammatory Protein-1 Alpha, a Potential Biomarker for Predicting Left Atrial Remodeling in Patients With Atrial Fibrillation.

Objectives: Left atrial (LA) remodeling itself is an independent risk factor for ischemic stroke and mortality, with or without atrial fibrillation (AF). Macrophage inflammatory protein-1 alpha (MIP-1α) has been reported to be involved in the induction of autoimmune myocarditis and dilated cardiomyopathy. Little is known about whether MIP-1α can be used to predict LA remodeling, especially in patients with AF.Methods: We prospectively enrolled 78 patients who had received a cardiac implantable electronic device due to sick sinus syndrome in order to define AF accurately. AF was diagnosed clinically before enrollment, according to 12-lead electrocardiography (ECG) and 24-h Holter test in 54 (69%) patients. The serum cytokine levels and the mRNA expression levels of peripheral blood leukocytes were checked and echocardiographic study was performed on the same day within 1 week after the patients were enrolled into the study. The 12-lead ECG and 24-h Holter test were performed on the same day of the patients' enrollment, and the device interrogation was performed every 3 months after enrollment. The enrolled patients were clinically followed up for 1 year.Results: There was no difference in baseline characteristics, cytokine levels and mRNA expression between patients with and without AF. Larger LA volume was positively correlated with higher levels of MIP-1α (r = 0.461, p ≤ 0.001) and the atrial high-rate episodes (AHREs) burden (r = 0.593, p < 0.001), and negatively correlated with higher levels of transforming growth factor (TGF)-β1 (r = −0.271, p = 0.047) and TGF-β3 (r = −0.279, p = 0.041). The higher AHREs burden and MIP-1α level could predict LA volume independently. The mRNA expression of RORC was negatively associated with the MIP-1α level.Conclusions: This study showed that higher MIP-1α was significantly associated with LA remodeling and may have the potentials to predict LA remodeling in terms of a larger LA volume, and that circadian gene derangement might affect the expression of MIP-1α.

25 Atrial remodelling in patients affected by chronic heart failure in therapy with sacubitril/valsartan

Abstract Aims Left atrial (LA) enlargement has been demonstrated to be a predictor of adverse cardiovascular outcomes, such as atrial fibrillation (AF), heart failure (HF), and cardiovascular death. Previous studies showed left ventricle ejection fraction (LVEF) improvement and reverse remodelling can be achieved after therapy with sacubitril/valsartan in real-world settings. We sought to investigate the association between left atrial (LA) structural and functional remodelling in patients with chronic HF after therapy with sacubitril/valsartan. Methods and results Patients affected by chronic HF with LV dysfunction (LVEF &amp;lt; 35%), NYHA functional class II–III were followed up between September 2019 and March 2020. All patients underwent clinical and echocardiography Follow-up at baseline and after 6 months of therapy with sacubitril/valsartan. Measures of LA structure [LA end-systolic volume (LAESV)] and function [left atrial emptying fraction (LAEF), peak atrial longitudinal strain (PALS), LA conduit strain and peak atrial contraction strain (PACS)] were calculated. A total of 47 patients (median age 66 ± 7.97, male gender 85%, mean LVEF 28.33 ± 5.61%) were enrolled. The left atrial strain parameters (PALS and LA conduit) resulted higher at 6 months follow-up respect to baseline values, (14.68 ± 7.16 vs. 18.67 ± 8.03, P &amp;lt; 0.001, and −7.61 ± 4.07 vs. −9.71 ± 5.23, P = 0.007, respectively). Conclusions Treatment with sacubitril/valsartan in patients with HFrEF is associated with an improvement in LA functional remodelling in a real-world scenario.

Characteristics of left atrial remodeling in patients with atrial fibrillation and hypertrophic cardiomyopathy in comparison to patients without hypertrophy

Atrial fibrillation (AF) leads to remodeling characterized by changes in both size and shape of the left atrium (LA). Here we aimed to study the effect of hypertrophic cardiomyopathy (HCM) on the pattern of LA remodeling in AF-patients. HCM-patients (n = 23) undergoing AF ablation (2009–2012) were matched and compared with 125 Non-HCM patients from our prospective registry. Pre-procedural CT data were analyzed (EnSite Verismo, SJM, MN) to determine the maximal sagittal (anterior–posterior, AP), coronal (superior-inferior, SI and transversal, TV) dimensions and the sphericity index (LAS). Volume (LAV) was rendered after appendage (LAA) and pulmonary vein (PV) exclusion. A cutting plane, between PV ostia/LAA and parallel to the posterior wall, divided LAV into anterior- (LA­A) and posterior-LA (LA­P) parts. The ratio LA-A/LAV was defined as asymmetry index (ASI). HCM patients had a wider inter-ventricular septum and a smaller LV than Non-HCM patients. LA volume (LAV 166 ± 72 vs. 130 ± 36 ml, p = 0.03) and LA diameters were significantly larger in HCM patients. Anterior volume (LA-A: 112 ± 48 vs. 83 ± 26 ml, p < 0.001) differed significantly between groups, whereas the posterior volume LA-P (55 ± 28 vs. 47 ± 13 ml, p = 0.23) and LAS (75% vs. 78%, p = 0.089) was similar in both groups. As a result, ASI was significantly higher (67 ± 6 vs. 63 ± 6%, p = 0.01) in HCM than in Non-HCM patients. In conclusion, LA remodeling in patients with AF and HCM is characterized by asymmetric dilatation, driven by an anterior rather than a posterior dilatation. This can be characterized by three-dimensional imaging and could be used as surrogate of advanced atrial remodeling.

Left and right atrial appendage functional features as predictors for voltage-defined left atrial remodelling in patients with long-standing persistent atrial fibrillation

It was hypothesised that left atrial (LA) fibrosis identified by the presence of low-voltage areas (LVA) may influence the mechanical and electrical function of the left (LAA) and right (RAA) atrial appendage among the long-standing persistent atrial fibrillation (LSPAF) population. 140 consecutive patients underwent voltage mapping of LA with a multielectrode catheter following pulmonary vein isolation and restoration of sinus rhythm with cardioversion. Echocardiography determined LAA peak outflow and inflow velocities and intracardiac catheter-based mean LAA and RAA AF cycle length (AFCL) were obtained during AF before ablation. The impact of flow velocities and AFCL on the prevalence and location of LVA was further evaluated. LVA were detected in 54% of the patients. 14% of the patients presented severe global LVA burden > 20% of the total LA surface area. 29% of the patients presented a disseminated pattern of remodelling as 3 out of 5 LA segments were affected. LAA AFCL, RAA AFCL, LAA flow velocities did not predict the absolute presence of LVA. However LAA AFCL > 155 ms predicted disseminated LVA pattern and LAA AFCL > 165 ms severe LVA incidence. LAA AFCL > 155 ms was predictive for existence of LVA within antero-septal LA segments whilst LAA emptying velocity ≤ 0.2 m/s within lateral wall. Moreover RAA AFCL > 165 ms was strongly related to the presence of LAA AFCL > 15 ms and > 165 ms. LAA and RAA functional assessment was predictive of the presence of advanced stages of voltage-defined LA fibrosis and its regional distribution among LSPAF population

THE NEW GENETIC ASPECTS OF ATRIAL FIBRILLATION IN PERSONS OF THE RUSSIAN POPULATION

Atrial fibrillation (AF) is one of the most common and dangerous heart rhythm disorders. Lone AF is due to a genetic predisposition. Foreign studies have proven the association of rs2200733 polymorphism of chromosome 4q25 with AF. No such studies have been conducted in the Russian Federation. Purpose of the study: to determine the association of the rs2200733 polymorphism of chromosome 4q25 with the development of AF, and to exclude the possible connection of the studied polymorphic marker with concomitant cardiovascular pathology. A total of 247 patients with AF were examined (113 from lone AF, 134 from secondary). Control group - 182 healthy people. Behavior: ECG, EchoCG, Holter ECG monitoring, blood test for thyroid hormones, VEM, CAG, molecular genetic research. In the group of patients with AF, the TT genotype was detected in 12.95%, which is statistically significant more often than in the control group (4.94%), p&lt;0.05. In the presence of a genotype with a rare T allele, the risk of developing AF increases by 1.5 times. The TT genotype was statistically significant more often in the subgroup of patients with isolated AF (17.70%) in comparison with the control group (4.94%), p&lt;0.05. The risk of developing isolated AF in the presence of a genotype with a rare allele T is 1.8 times increased. Chronic heart failure, no statistically significant differences were found (p&gt;0.05). In patients with the TT genotype, the mean LA size was 3.738 ± 0.494 cm, it was statistically significantly smaller than in patients with the CC genotype, which corresponded to 3.925 ± 0.629 cm, p&lt;0.05; and than in individuals with a heterozygous CT genotype, its value in this subgroup is 4.018 ± 0.639 cm, p&lt;0.05. Conclusions: Homozygous genotype for the rare TT allele and the T allele of the rs2200733 polymorphism of chromosome 4q25 are predictors of lone AF. The rs2200733 polymorphism has no association with any cardiovascular pathology, such as hypertension, ischemic heart disease and chronic heart failure. The TT genotype and the T allele of the rs2200733 polymorphism do not affect left atrial remodeling in patients with AF.

The effect of left atrial remodeling after cryoballoon ablation and radiofrequency ablation for paroxysmal atrial fibrillation.

BackgroundCryoballoon ablation (CBA) and radiofrequency ablation (RFA) are the most common procedures used to treat refractory atrial fibrillation (AF) and are performed through pulmonary vein isolation (PVI). Studies have shown that CBA can approximately match the therapeutic effects of RFA against AF. However, few studies have investigated the difference between CBA and RFA of the effects on left atrial remodeling for paroxysmal AF.ObjectiveAtrial remodeling is considered pivotal to the occurrence and development of AF, therefore we sought to assess the influence of atrial remodeling in patients with paroxysmal AF after CBA and RFA in this study.MethodsIn this nonrandomized retrospective observational study, we enrolled 328 consecutive patients who underwent CBA or RFA for refractory paroxysmal AF in May 2014 to May 2017 in our hospital. After propensity score matching, 96 patients were included in the CBA group, and 96 were included in the RFA group. Patients were asked to undergo a 12‐lead electrocardiogram, a 24‐h Holter monitor, and an echocardiogram and to provide their clinical history and symptoms at 6 months and 1, 2, and 3 years postprocedurally. Electrical remodeling of the left atrium was assessed by P wave dispersion (Pdis); structural remodeling was assessed by the left atrium diameter (LAD) and left atrial volume index (LAVI) during scheduled visits.ResultsAs of January 2020, compared with baseline, at 1 year, 2 years, and 3 years after ablation, the average changes in Pdis (∆Pdis), LAD (∆LAD), and LAVI (∆LAVI) were significant in both the CBA and RFA groups. Six months after ablation, ∆Pdis, ∆LAD, and ∆LAVI were greater in the CBA group than in the RFA group. There was no significant difference between the two groups in AF/flutter recurrence, but the AF/flutter‐free survival time of CBA group may be longer than RFA group after 2 years after ablation. A higher ∆Pdis, ∆LAD, or ∆LAVI at 1 year after ablation may increase AF/flutter‐free survival.ConclusionsAlthough CBA and RFA are both effective in left atrial electrical and structural reverse‐remodeling in paroxysmal AF, CBA may outperform RFA for both purposes 6 months after ablation. However, during long‐term follow‐up, there was no significant intergroup difference.

THE ROLE OF INFLAMMATION AND COAGULATION CASCADE IN THE PATHOGENESIS OF ATRIAL FIBRILLATION

Introduction: Atrial fibrillation (AF) is associated with prothrombotic or hypercoagulable states, various inflammation markers such as interleukin-6 (IL-6) and hsC-reactive protein (hsCRP) have also been associated with AF. The aim of this study is to investigate the relationship between inflammation markers and the prothrombotic state in the setting of AF and the impact on outcome in patients with AF. Methods: We observed 141 patients with non-valvular AF. As a control group patients similar in gender and age without AF were examined. Clinical, instrumental and laboratory tests were performed on the observed patients. The markers of the coagulation cascade (TF and F) and of inflammatory markers (hsCRP and IL-6) were studied additionally by ELISA on the analyzer "Stat Fax 303 Plus". Studies were conducted using SPSS 13.0 and EXCEL-2013. Results: The obtained results showed that compared to the control group, AF patients had significantly higher levels of IL-6 (p = 0.043), hsCRP (p = 0.002), TF (p = 0.026), and F (p = 0.025). Moreover, levels of hsCRP were higher among AF patients at "high" risk of stroke by CHA2DS2-VASc Score (p = 0.003). Besides, the levels of hsCRP and IL-6 were markedly elevated in patients with dilated left atrium (p = 0.001), poorly functioning left atrial appendage (p = 0.023) and longer duration of AF (p = 0.002). Conclusion: We have demonstrated that the increased plasma levels of IL-6 and hsCRP are related to indices of the coagulation cascade and contribute to structural atrial remodeling in patients with AF.

Atrial arrhythmias in patients with left ventricular assist devices.

Atrial arrhythmias commonly occur in patients with advanced heart failure with reduced ejection fraction (HFrEF) who require left ventricular assist devices (LVADs) implantation. This review summarizes the current literature regarding the incidence, prevalence, and predictors of atrial arrhythmias in LVAD patients and its impact on the clinical outcomes. Moreover, we review the mechanisms and management strategies of atrial arrhythmias in this population. Atrial arrhythmias including atrial fibrillation, atrial flutter, and atrial tachycardia are highly prevalent in patients with advanced HFrEF before or after the LVAD implantation. Atrial arrhythmias have a significant impact on overall clinical outcome including survival, heart failure hospitalization, quality of life, thromboembolic events and resource utilization. Atrial fibrillation and other atrial arrhythmias frequently coexist in this population. In patients with atrial arrhythmias and LVAD, anticoagulation and cardiovascular implantable electronic devices should be closely monitored and managed to prevent thromboembolic events or inappropriate shocks. Rhythm and rate control strategies are comparable regarding overall clinical outcomes in this population. LVADs induce favorable atrial remodeling in patients with HFrEF. Atrial arrhythmias are highly common in LVAD patients and have significant impact on overall clinical outcomes. Further studies are needed to determine optimal management and prevention of atrial arrhythmias in LVAD population.

Circulating Stromelysin-1 (MMP-3): A potential predictor for atrial fibrillation in patients with mitral stenosis

The mitral valvular disease is strongly related to atrial fibrillation (AF). The impact of matrix metalloproteinases (MMPs) on structural atrial remodeling and sustainment of AF in patients with AF is unresolved. This study aimed to investigate serum metalloproteinases as markers of atrial remodeling in patients with mitral stenosis. Blood sample, clinical and echocardiographic parameters were evaluated in 73 patients with mitral stenosis: 37 with AF and 36 with sinus rhythm. The Plasma levels of MMP-3, MMP-2, MMP-9 and TIMP-1 were measured by ELISA sandwich assay. The concentration of MMP-3 ( P = 0.05) was significantly higher in patients with AF than in patients with sinus rhythm. After adjusting for age, gender, and treatment, the regression model indicates that the high MMP-3 appears to be a risk factor for AF (OR = 1.5, P = 0.001). ROC curve showed that plasma levels of MMP-3 can be predict atrial remodeling in patient with mitral stenosis at the cutoff value of > 9.05 ng/ml with an area under the curve (AUC = 0.618, P = 0.038). The combined analysis with the receiver-operating curve of matrix parameters shows a strong association with AF where we observed an increased area (0.706, P = 0.004). Elevated level of MMP-3 was related to the occurrence of AF. This suggests that MMP-3 could be a marker of atrial remodeling in patients with AF.

364 Left Atrial Cross Sectional Area as a Measure of Left Atrial Remodelling in Patients With Hypertension and Diabetes.

364 Left Atrial Cross Sectional Area as a Measure of Left Atrial Remodelling in Patients With Hypertension and Diabetes.

P5740ACE2 activity level is associated with embolic stroke of undetermined source

Abstract Background ACE2 activity levels correlate with adverse left atrial remodelling in patients with atrial fibrillation (AF). Several biochemical and structural markers have been associated with embolic stroke of undetermined source (ESUS). The relationship between ACE2 activity and ESUS is unknown. Purpose Randomised controlled trials failed to demonstrate a clear benefit of oral anticoagulation in an unselected ESUS population. As selective use of oral anticoagulation guided by biomarker risk-profiling may benefit these patients, we evaluated the association between ACE2 activity and ESUS. Methods This prospective case control study compared patients with ESUS against a control group matched for vascular risk factors. ESUS was diagnosed following cerebral vascular imaging and 24 hours of cardiac monitoring to exclude AF. Blood samples were collected for measurement of ACE2 activity, D-Dimer and high sensitivity troponin T (hsTnT). Results A total of 51 patients in the ESUS group were compared with 47 patients in the Control group. ACE2 activity and D-Dimer levels were significantly higher in the ESUS group. There was a significant but weak positive correlation between ACE2 activity and hsTnT (r=0.20, p&lt;0.05). Left atrial volume index (LAVI) on echocardiography was significantly higher in the ESUS group. On regression modelling adjusting for LAVI, only ACE2 activity remained significant for ESUS, with a 20% rise in odds for every 4 unit increase in ACE2 activity (OR 1.20; 95% CI: 1.01 - 1.36, p=0.04). Participant characteristics Control (n=47) ESUS (n=51) P value Age (years) 65.65±6.78 67.20±6.89 0.26 Female gender 22 (45.8) 19 (38.0) 0.43 Hypertension 22 (45.8) 24 (48.0) 0.83 Diabetes mellitus 9 (18.8) 12 (24.0) 0.53 CHA2DS2VASc score 2 (1–3) 2 (1–3) 0.50 LA size &amp; Biomarkers LA volume index (ml/m2) 36.5 (32.6–42.5) 39.1 (36.2–46.0) 0.04 ACE2 (pmol/ml/min) 7.24 (2.66–14.64) 10.16 (4.54–18.80) 0.04 D-Dimer (mg/L) 0.35 (0.3–0.5) 0.40 (0.30–0.60) 0.02 hsTroponin T (ng/L) 7.0 (5–10) 9.00 (6.0–13.5) 0.05 Values are expressed as mean ± standard deviation, median (IQR), or n (%). Median ACE2 activity Conclusion(s) ACE2 activity is associated with ESUS independent of left atrial volume and correlate with elevated Troponin. Further studies are warranted to investigate the utility of ACE2 activity in identifying ESUS patients that may benefit from oral anticoagulation. Acknowledgement/Funding This study received project funding from the Eastern Health Foundation

Impact of Age and Left Atrial Remodeling in Patients with Atrial Fibrillation Undergoing Left Ventricular Assist Device Implantation

Objective Patients with advanced heart failure (AHF) undergoing left ventricular assist device have a high prevalence of atrial arrhythmias. Moreover, patients with AHF have significant left atrial remodeling that increases their risk for mortality. The objective of this study was to evaluate the impact of left atrial volume index (LAVI) on mortality in LVAD patients with atrial fibrillation (AF). Methods A total of 159 consecutive patients undergoing LVAD implantation were analyzed retrospectively. Median follow up was for 2.0 years. Electronic medical records, electrocardiograms, echocardiograms, and invasive hemodynamics were reviewed. The associations of AF and LAVI with all-cause mortality were examined using Kaplan-Meier survival analysis and Cox proportional hazard regression. Results We measured LAVI size in those with and without AF. LAVI size was categorized into small or large based on a median value of 54.1 ml/m2. Patients with AF/Large LAVI were older, had higher prevalence of diabetes, larger end diastolic dimension, larger end diastolic volume and significant valvular heart disease compared to no AF/small LAVI group. (Table). Survival estimate showed increased mortality in those with AF/large LAVI compared to those with no AF/small LAVI (p&lt0.037) (Figure). Univariate analysis showed that age (RR: 1.037, 95%CI:1.008-1.068, p=0.012) and LAVI (RR: 1.016, 95% CI:1.002-1.030, p=0.026) were the only predictors for mortality. After multivariate analysis however, only age (age-RR: 1.039, 95% CI:1.004-1.075, p=0.027 vs. LAVI-RR: 1.004, 95% CI:0.987-1.022, p=0.653) was determined to be a predictor of mortality. Conclusions LVAD patients with history of atrial fibrillation and large LAVI size are at higher risk for mortality, however this effect may be attributable to older age rather than changes in left atrial remodeling and presence of AF.

TGFβ1 and HGF regulate CTGF expression in human atrial fibroblasts and are involved in atrial remodelling in patients with rheumatic heart disease.

ObjectiveThis study aimed to investigate the effects of transforming growth factor β1 (TGF β1) and hepatocyte growth factor (HGF) on the expression of connective tissue growth factor (CTGF) in human atrial fibroblasts, and to explore the relationship of these factors in atrial fibrosis and atrial anatomical remodelling (AAR) of patients with atrial fibrillation (AF).MethodsFresh right auricular appendix tissue of 20 patients with rheumatic heart disease undergoing valve replacement surgery was collected during surgeries, 10 patients had sinus rhythm(SR), and 10 patients had chronic atrial fibrillation (CAF). Atrial fibroblasts were then cultured from the tissues with differential attachment technique and treated with either TGFβ1 (10 ng/mL) or HGF (100 ng/mL). CTGF mRNA levels were measured by RT‐PCR, and CTGF protein content was determined using immunofluorescence and Western blotting assays.ResultsCAF group had higher left atrial diameters (LADs) and higher CTGF mRNA expression in atrial fibroblasts compared with SR group. The CTGF protein content in CAF group was higher than that of SR group and positively correlated with LAD and AF duration. After CAF group was treated with TGFβ1, CTGF mRNA and protein expression were significantly down‐regulated, whereas when treated with HGF, expression was up‐regulated compared with SR group.ConclusionsIncreased CTGF expression was associated with enlarged LAD, atrial fibrosis and AAR in patients with AF. TGFβ1 and HGF regulate CTGF expression in human atrial fibroblasts with up‐regulation of mRNA and down‐regulation of protein, therefore, either promote or inhibit atrial fibrosis, which could be related to the incidence and persistence of AF.

Elevated Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity is Associated with Embolic Stroke of Undetermined Source

Background: ACE2 activity levels correlate with adverse left atrial remodelling in patients with atrial fibrillation (AF). Several biochemical and structural markers have been associated with embolic stroke of undetermined source (ESUS). We investigated the relationship between ACE2 activity and ESUS. Methods: This prospective case control study compared patients with ESUS against a control group matched for vascular risk factors. ESUS was diagnosed following cerebral and carotid vascular imaging and 24 hours of cardiac monitoring to exclude AF. Blood samples were collected for measurement of ACE2 activity, D-Dimer and high sensitivity troponin T (hsTnT). Results: Fifty-one ESUS patients (67 ± 7 years, CHA2DS2-VASc score 2) were compared with 47 control patients (66 ± 7 years, CHA2DS2-VASc score 2). Median ACE2 activity (10 pmol/min/ml vs. 7 pmol/min/ml, p < 0.05) and D-Dimer levels (0.40 mg/L vs 0.35 mg/L, p < 0.05) were significantly higher in the ESUS group. There was a significant but weak positive correlation between increased ACE2 activity and hsTnT (r = 0.20, p < 0.05). Left atrial volume index (LAVI) on echocardiography was significantly higher in the ESUS group (40 ml/m2 vs 36 ml/m2, p < 0.05). On regression modelling, adjusting for LAVI, only ACE2 activity (OR 1.04, CI: 1.002–1.09; p < 0.05) remained significant for ESUS. Conclusion: ACE2 activity levels are associated with ESUS, independent of LAVI. Further studies are warranted to investigate whether ACE2 activity can identify ESUS patients that may benefit from oral anticoagulation.

Initial bi atrial three-dimensional echocardiographic evaluation in non-valvular atrial fibrillation according to rhythm outcome at six month follow-up

Two-dimensional left atrial (LA) size is an independent echocardiographic predictor of atrial fibrillation (AF) occurrence and recurrence. Our study aimed to evaluate LA and right atrial (RA) three-dimensional (3D) volumes at admission (M0) in patients with AF to define atrial remodeling according to rhythm outcome at 6 month follow-up (M6). 3D RA and LA parameters were assessed at M0 in patients admitted for AF: body surface area-indexed maximum 3D volume (Max 3D RA Voli, Max 3D LA Voli) and indexed minimum volume (Min 3D RA Voli, Min 3D LA Voli); atrial emptying fraction (3D RAEF, 3D LAEF) and atrial expansion index (3D RAEI, 3D LAEI). Forty-eight consecutive patients hospitalized for AF were prospectively included. Two groups were individualized according to rhythm outcome: successful cardio version (SuccCV) in 35(72.9%) patients including either spontaneous ( n = 10) or electrical cardioversion ( n = 25) (AF at M0 and sinus rhythm (SR) at M6); failure or contra indication to cardioversion (FailCV) in 13(27.1%) patients (AF at M0 and AF at M6). 3D echocardiographic evaluation from 41 patients at M0 found: – significantly upper Min 3D RA Voli, Min 3D LA Voli in group FailCV in comparison with SuccCV; – significantly lower 3D RAEF, 3D RAEI, 3D LAEF, 3D LAEI in group FailCV in comparison with SuccCV; – no significant differences regarding Max 3D RA Voli, Max 3D LA Voli between groups FailCV and SuccCV ( Table 1 ). 3D atrial echocardiographic parameters could be useful to predict initial atrial remodelling in patients admitted for AF.

Profibrotic, Electrical, and Calcium-Handling Remodeling of the Atria in Heart Failure Patients With and Without Atrial Fibrillation.

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases that often co-exist. Animal models have suggested complex AF-promoting atrial structural, electrical, and Ca2+-handling remodeling in the setting of HF, but data in human samples are scarce, particularly regarding Ca2+-handling remodeling. Here, we evaluated atrial remodeling in patients with severe left ventricular (LV) dysfunction (HFrEF), long-standing persistent (‘chronic’) AF (cAF) or both (HFrEF-cAF), and sinus rhythm controls with normal LV function (Ctl) using western blot in right-atrial tissue, sharp-electrode action potential (AP) measurements in atrial trabeculae and voltage-clamp experiments in isolated right-atrial cardiomyocytes. Compared to Ctl, expression of profibrotic markers (collagen-1a, fibronectin, periostin) was higher in HFrEF and HFrEF-cAF patients, indicative of structural remodeling. Connexin-43 expression was reduced in HFrEF patients, but not HFrEF-cAF patients. AP characteristics were unchanged in HFrEF, but showed classical indices of electrical remodeling in cAF and HFrEF-cAF (prolonged AP duration at 20% and shorter AP duration at 50% and 90% repolarization). L-type Ca2+ current (ICa,L) was significantly reduced in HFrEF, cAF and HFrEF-cAF, without changes in voltage-dependence. Potentially proarrhythmic spontaneous transient-inward currents were significantly more frequent in HFrEF and HFrEF-cAF compared to Ctl, likely resulting from increased sarcoplasmic reticulum (SR) Ca2+ load (integrated caffeine-induced current) in HFrEF and increased ryanodine-receptor (RyR2) single-channel open probability in HFrEF and HFrEF-cAF. Although expression and phosphorylation of the SR Ca2+-ATPase type-2a (SERCA2a) regulator phospholamban were unchanged in HFrEF and HFrEF-cAF patients, protein levels of SERCA2a were increased in HFrEF-cAF and sarcolipin expression was decreased in both HFrEF and HFrEF-cAF, likely increasing SR Ca2+ uptake and load. RyR2 protein levels were decreased in HFrEF and HFrEF-cAF patients, but junctin levels were higher in HFrEF and relative Ser2814-RyR2 phosphorylation levels were increased in HFrEF-cAF, both potentially contributing to the greater RyR2 open probability. These novel insights into the molecular substrate for atrial arrhythmias in HF-patients position Ca2+-handling abnormalities as a likely trigger of AF in HF patients, which subsequently produces electrical remodeling that promotes the maintenance of the arrhythmia. Our new findings may have important implications for the development of novel treatment options for AF in the context of HF.