Left Atrial Appendage Flow Velocity Research Articles

Sinus rhythm maintenance and the changes of echocardiographic parameters in patients with late persistent atrial fibrillation at 6 months after direct current cardioversion

Abstract Background Late persistent non-valvular atrial fibrillation (AF), with a duration of its episode ≥90 days and up to 12 months, is considered a distinct persistent AF entity, which might possess substantial differences as compared to its early persistent pattern (up to 3 months) in terms of myocardial remodeling and its reversibility after cardioversion. Purpose To study the changes of echocardiographic parameters in patients with non-valvular late persistent AF with respect to sinus rhythm (SR) maintenance at 6 months after successful direct current cardioversion (DCCV). Methods The cohort single-center study enrolled 59 late persistent AF patients, who underwent a successful elective DCCV. At 6-months follow-up, patients were subdivided into the groups regarding SR maintenance: 32 (54 %%) patients with a maintained SR (G1), and 27 (46 %) patients with a failure to maintain SR (G2). The parameters of myocardial remodeling and function were evaluated by transthoracic (TTE) and transesophageal echocardiography (TEE) baseline (by TTE and TEE) and at 6-months follow-up (by TTE). Results TTE data from G1 patients, in contrast to G2, suggested better baseline status of left heart chambers, particularly the lower diameter of left atrium (LA), left ventricular (LV) end-diastolic and end-systolic volumes and higher LV systolic function (by LV ejection fraction [EF]). According to the TEE data, G2 (vs. G1) was characterized by more prevalent cases of LA spontaneous (echo) contrast (41 % vs. 15 %, respectively; p=0,042) and LA appendage flow velocity ≤40 cm/s (82 % vs. 53 %, respectively; p=0,022). At 6-months follow-up TTE, G1 patients, as opposed to G2, demonstrated a better profile of echocardiographic parameters, namely a lower LA diameter, LA and right atrium (RA) volumes, along with less advanced LV remodeling and higher LV EF. TTE data from G1 at 6-months follow-up after DCCV suggested the reverse remodeling of both atria, namely the decrease of LA diameter, LA volume and its index (Fig. 1), as well as RA volume and its index. Moreover, G2 demonstrated a decline in LV systolic function, in particular the rise of LV end-systolic volume and decrease of LV EF (Fig. 2), as compared to G1. Furthermore, at 6-months follow-up, G2 patients presented with more advanced severity of PH and tricuspid regurgitation, in comparison with G1. Conclusions Late persistent AF patients with a SR maintenance at 6-months follow-up after successful DCCV presented a better baseline profile of myocardial remodeling and systolic function. The SR maintenance at 6-months follow-up after DCCV was associated with the reverse remodeling of left heart chambers (LA and LV) and RA. On the contrary, a failure to maintain SR in late persistent AF patients was associated with a deterioration in LV systolic function, and more advanced PH and tricuspid regurgitation.

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0-2

Abstract Background Even in patients with atrial fibrillation (AF) and low CHA2DS2-VASc scores, it is not always possible to completely rule out left atrial appendage (LAA) thrombus. Further stratification of the risk of LAA thrombosis in these patients remains an important yet unresolved issue. Left ventricular hypertrophy (LVH) is a prognostic risk factor in AF and has been associated with a worse prognosis, particularly in those with low CHA2DS2-VASc scores. Purpose To investigate the clinical significance of echocardiographic LVH for risk stratifying LAA thrombogenic milieu as a surrogate for cardioembolic risk in patients with AF and CHA2DS2-VASc scores of 0–2. Methods This was a single-center, retrospective study. We enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0–2 who underwent transesophageal echocardiography. The patients were divided into two groups based on the presence or absence of LVH. Owing to the racial differences in normative left ventricular mass index (LVMI) reference values, LVH was defined in this study using Japanese reference values. LVH was defined as LVMI ≥108 g/m2 for men and ≥98 g/m2 for women. LAA thrombogenic milieu was defined by any of the following findings: (1) thrombus, (2) severe spontaneous echo contrast or sludge, or (3) average LAA flow velocity ≤20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium (LA) were obtained using transthoracic echocardiography. Results The mean age was 61 ± 10 years, and 12.2% were female. Overall, 77 (10.9%) patients were classified into the LVH group, and 41 (5.8%) of patients had LAA thrombogenic milieu. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH (32.5% vs. 2.5%, p<0.001). Figure 1 illustrates the details of the patients with the LAA thrombogenic milieu based on LVH presence and CHA2DS2-VASc scores. The LVH group included six patients with LAA thrombus, even with CHA2DS2-VASc scores of 2, whereas the non-LVH group had no patient with LAA thrombus. Table shows the association of LAA thrombogenic milieu and clinical and echocardiographic parameters by logistic regression analysis; LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and LA volume index). Moreover, LVH provided incremental prognostic value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and LA reservoir strains (p<0.001). These findings are summarized in Figure 2. Conclusion Echocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0–2.

Echocardiographic Assessment of Left Atrial Mechanics in Patients with Atrial Fibrillation Undergoing Electrical Cardioversion: A Systematic Review

Background: To date, only a few studies have evaluated left atrial (LA) mechanics in patients with atrial fibrillation (AF) scheduled for electrical cardioversion (ECV). The present systematic review has been primarily designed to summarize the main findings of these studies and to examine the overall effect of AF on left atrial reservoir strain (LASr) in patients undergoing ECV. Methods: All the echocardiographic studies evaluating the effect of AF on LA mechanics in patients scheduled for ECV, selected from the PubMed and EMBASE databases, were included. There was no limitation of time period. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: The full texts of 12 studies with 880 AF patients were analyzed. The pooled ECV success rate was 91.5% (range 65.8–100%). Over a median follow-up of 5.4 months (range 0.3–12 months), 35.2% of the patients (range 5–68.8%) experienced AF recurrence. At baseline, the average LASr was 11.4% (range 6.2–17.7%). A reduced LASr before ECV was strongly correlated with reduced left atrial appendage (LAA) flow velocities and/or thrombosis. The main independent predictors of cardioversion failure were impaired LASr and previous AF history. A severe LASr deterioration was independently correlated with AF recurrence after ECV. The other independent predictors of AR relapses were LA asynchrony, reduced difference between post- and pre-ECV LASr, and reduced right atrial reservoir strain. Conclusions: LASr assessment before ECV may provide useful prognostic information about AF relapses and improve the refinement of the thromboembolic risk of AF patients scheduled for ECV.

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0–2

BackgroundThe clinical significance of echocardiographic left ventricular hypertrophy (LVH) in risk stratification of left atrial appendage (LAA) thrombogenic milieu, as a surrogate for cardioembolic risk, in patients with atrial fibrillation (AF) and HA2DS2-VASc scores of 0–2 is unknown. Methods and resultsWe enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0–2 who underwent transesophageal echocardiography. LAA thrombogenic milieu was defined as the presence of a thrombus, severe spontaneous echo contrast, sludge in the LAA, or LAA flow velocity ≤ 20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium were obtained using transthoracic echocardiography. Among the 707 patients, 77 (10.9 %) exhibited LVH. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH group (32.5 % vs. 2.5 %, p < 0.001). LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and left atrium volume index) (odds ratio [OR]: 7.54, 95 % confidence interval [CI]: 3.49–16.29, p < 0.001 and OR: 7.16, 95 % CI: 3.26–15.73, p < 0.001, respectively). Moreover, LVH provided incremental value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and left atrium reservoir strains (p < 0.001). ConclusionEchocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0–2.

The soluble ST2 level predicts risk of atrial fibrillation recurrences in long-term period after radiofrequency ablation

Background and objectives:The hypothesis of the study was the assumption that the serum levels of soluble ST2 (sST2) and growth differentiation factor (GDF-15) can be predictors of atrial fibrillation (AF) recurrence in long-term period after primary radiofrequency catheter ablation (RFA).MethodsOf the 165 patients included in the prospective follow-up, the final analysis included 131 patients whose follow-up duration reached 18 months after the end of the blanking period (3 months after RFA). The median age of patients was 59.0 (50.0; 64.0) years, and 80 (61%) were men. Paroxysmal AF was present in 103 (79%) and persistent AF in 28 (21%) patients. All patients underwent transthoracic and transesophageal echocardiography, and electroanatomic mapping was used to assess the area of low-voltage zones (LVZ). sST2 and GDF-15 levels were determined by ELISA using GDF-15/MIC-1 analytical kits (BioVender, Czech Republic) and Presage ST2 (Critical Diagnostics, USA) before RFA. After RFA, patients had regular follow-up visits at 3-6-9-12-18 months with 12-lead ECG or Holter ECG monitoring and with clinical evaluation. The primary endpoint was the occurrence of the first symptomatic AF recurrence (AFr) lasting > 30 s, recorded on an ECG or during daily ECG monitoring, after a blanking period.ResultsAt the 18-month follow-up, 47 patients (35.9%) had AFr. The groups with and without AFr didn`t differ in the LVZ area. The medians of NT-proBNP, GDF-15 and sST2 also didn`t differ significantly between the groups, but in patients with AFr, the proportion of those with sST2 ≥ 36 ng/ml (the border of the lower and middle terziles) was higher (p = 0.03). According to the one-factor Cox regression analysis, AFr were associated with four factors: AF history ≥ 1 year, early AFr (during the blanking period), left atrial appendage flow velocity (LAAFV) < 54 cm/sec and sST2 ≥ 36 ng/ml. In the multivariate Cox analysis two independent predictors of AFr were obtained: sST2 ≥ 36 ng/ml (HR = 3.8; 95% CI 1.5–9.8, p = 0.006) and LAAFV < 54 сm/sec (HR = 1.96; 95% CI 1.01–3.82, p = 0.048).ConclusionsSerum sST2 level with a cut-off value of 36 ng/ml or more can be used as a predictor of AF recurrence in the long-term period after primary RFA.

Biomarcadores proteómicos para la predicción no invasiva de trombos en la orejuela izquierda de pacientes con fibrilación auricular

Introduction and objectivesThe CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment. MethodsDeep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification. ResultsThe LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices. ConclusionsProtein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.

Correlation between Anterior Mitral Annular Plane Systolic Excursion and Left Atrial Appendage Stasis in Patients with Nonvalvular Atrial Fibrillation.

Atrial fibrillation (AF) can lead to a decline in left atrial appendage (LAA) function, potentially increasing the likelihood of LAA thrombus (LAAT) and spontaneous echo contrast (SEC). Measuring LAA flow velocity through transesophageal echocardiography (TEE) is currently the primary method for evaluating LAA function. This study aims to explore the potential correlation between anterior mitral annular plane systolic excursion (aMAPSE) and LAA stasis in patients with non-valvular atrial fibrillation (NVAF). A total of 465 patients with NVAF were enrolled between October 2018 and November 2021. Transthoracic echocardiography (TTE) and TEE were performed before scheduled electrical cardioversion. Propensity score matching (PSM) was used to balance confounders between the groups with and without LAAT/dense SEC. Patients in the LAAT/dense SEC group showed increased left atrial (LA) diameter, LAA area, alongside reduced left ventricular ejection fraction (LVEF), LAA velocity, conjunction thickening ratio, aMAPSE, and LAA fraction area change (FAC) compared to those in the non-LAAT/dense SEC group. Multivariate logistic regression analysis identified aMAPSE and LAA FAC as independent predictors for LAAT/dense SEC. Specifically, an aMAPSE of 6.76 mm and an LAA FAC of 29.65% predicted LAAT/dense SEC with high diagnostic accuracy, demonstrated by an area under the curve (AUC) of 0.81 (sensitivity 0.81, specificity 0.80) for aMAPSE, and an AUC of 0.80 (sensitivity 0.70, specificity 0.84) for LAA FAC. Both aMAPSE and LAA FAC independently correlated with and accurately predict LAAT/dense SEC. Incorporating aMAPSE into routine TEE evaluations for LAA function alongside LAA flow velocity is recommended.

Left atrial appendage thrombus in patients with atrial fibrillation who underwent oral anticoagulation.

Electric cardioversion of atrial fibrillation (AF) is associated with an increased risk of embolism, with embolic material existing in the heart cavities. The initiation of oral anticoagulation therapy reduces the risk of thromboembolic events. The aims of this study were to evaluate the prevalence of left atrial appendage (LAA) thrombi in non-valvular AF, to compare vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) with respect to thrombus prevalence, and to evaluate the rate of LAA thrombus persistence on repeat transesophageal echocardiography (TEE) after treatment change. We enrolled 160 consecutive AF patients who presented with an AF duration > 48 h and had undergone TEE before cardioversion. Left atrial appendage thrombus was observed in 12 (7.5%) patients, and spontaneous echo contrast 4 was observed in 19 (11.8%) patients; the incidence was similar between the NOAC and VKA groups (8.9% vs. 3.6% and 12.4% vs. 18.5 %, respectively). Among patients on NOAC, thrombus prevalence was detected in 8.4% of users of rivaroxaban, 8% of users of dabigatran, and 12.5% of users of apixaban. The LAA thrombus developed in 7.5% of patients despite anticoagulation therapy, demonstrating similar prevalence rates among patients either on NOAC or VKA. Lower mean LAA flow velocity and a history of vascular disease were independent predictors of embolic material in the LAA. It seems that in the case of embolic materials in LAA under NOAC treatment, switching to VKA provides additional clinical benefit to the patients.

Correlation between left atrial appendage morphology based on fractal dimension quantification and its hemodynamic parameters in patients with atrial fibrillation

To investigate the relationship between left atrial appendage (LAA) morphology, quantified based on fractal dimension (FD), and LAA hemodynamic parameters in patients with atrial fibrillation (AF), in an effort to reveal the effect of LAA shape on blood flow. 225 patients with AF who underwent cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) were enrolled. LAA morphology was quantified based on FD on cardiac CTA images, and LAA hemodynamic parameters, including injection fraction (EF), filling peak flow velocity (FV), maximum speed of emptying (PEV), and wall motion velocity (WMV), were assessed using TEE. We divided the patients with AF into two groups based on a mean LAA FD of 1.32: the low FD group (n=124) and the high FD group (n=101). Compared to the low FD group, there were more patients with LAA circulatory stasis/thrombus (P=0.008) in the high FD group, as well as lower LAA FV (P=0.004), LAA PEV (P=0.007), and LAA WMV (P=0.007). LAA FD was an independent and significant determinant of LAA EF (β=-11.755, P=0.001), LAA FV (β=-17.364, P=0.004), LAA PEV (β=-18.743, P<0.001), and LAA WMV (β=-7.740, P=0.001) in multiple linear regression analysis. LAA FD is an essential determinant of LAA hemodynamic parameters, suggesting that the relatively complex morphology of the LAA may influence its hemodynamics, which can correlate with embolic events.

Clinical and instrumental factors associated with sinus rhythm maintenance following direct current cardioversion of late persistent non-valvular atrial fibrillation at 6-months follow-up

Abstract Purpose To study the clinical and instrumental factors, associated with sinus rhythm (SR) maintenance following direct current cardioversion (DCCV) in patients with late persistent non-valvular atrial fibrillation (AF) at 6-months follow-up. Methods The cohort single-center study analyzed clinical and instrumental data from 59 late persistent AF patients (with duration of its episode ≥90 days [up to 12 months]), who underwent an elective DCCV. At 6-months follow-up, 32 (54 %%) patients succeeded to maintain SR, in contrast to 27 (46 %) patients with a failure to its maintenance. Results The univariate logistic regression analysis revealed, that the absence of heart failure (HF) stage C (i.e., the presence of its stage B), the higher left ventricular ejection fraction (LVEF) (by transthoracic echocardiography [TTE]), left atrial appendage flow velocity (LAAFV) &amp;gt;40 cm/s and the freedom from left atrial spontaneous echo contrast (LASEC) (by transesophageal echocardiography), ‒ all were associated with the higher chance to maintain SR at 6-months follow-up (Figure). At the same time, the higher baseline left atrial dimension (LAD) and more advanced pulmonary hypertension (PH) (by TTE) were associated with the failure of its maintenance to be more probable (Figure). At multivariate analysis, the following predictors of SR maintenance after DCCV at 6-months follow-up were identified: higher LVEF (OR 1,07 (95 % CI 1,01-1,13); р=0,021); LAAFV &amp;gt;40 cm/s (OR 4,33 (95 % CI 1,06-17,78); р=0,042), and less advanced PH (OR 0,24 (95% CI 0,06-0,93); р=0,038). Conclusion Better LV systolic function, LAAFV &amp;gt;40 cm/s and less advanced PH were the predictors of SR maintenance following DCCV in patients with late persistent (with duration of its episode ≥90 days) non-valvular AF at 6-months follow-up.

Validation of CT in comparison to TEE in routine workflow for detection of LAA thrombus in patients under oral anticoagulation presenting for left atrial ablation

Abstract Background Left atrial (LA) thrombus in patients (pts) presenting for LA ablation is an absolute contraindication to ablation. Although thrombi can still form despite the use of oral anticoagulation (OAC) in advance of the procedure. Transesophageal echocardiography (TEE) has been considered the gold standard for LAA thrombus detection. Additional cardiac computer tomography (CT) is often performed in pts with persistent atrial fibrillation (AF) or atrial tachycardia (AT). The aim of the study was in routine workflow 1) to identify the incidence of LAA thrombi in TEE and CT, 2) to search for an association in detecting LAA thrombi in the 2 methods and 3) to find out if the LAA flow velocity/ LA volume influences the thrombus detection. Methods Between 05/2018 and 10/2023 patients with AF/AT under OAC which were scheduled for a LA ablation were included. TEE and CT searching for LAA thrombus were carried out at intervals of up to 7 days. LAA flow velocity measured in the TEE. The LA volume which included LAA and excluded the pulmonary veins were obtained from the CT at the end-systole. Results Patients characteristics: 283 pts were included, mean age of 66y (+9y), 182 male, mean CHA2DS2-VASc score 3 [0-7]. All patients, mostly on NOACs (n=265), were orally anticoagulated. Mean LA volume (LA + LAA) was 158 ml (+45ml), LAA flow velocity was reduced (&amp;lt; 40 cm/s) in 119 pts (42%). In the majority of cases (73%), TEE and CT were performed at the same day or with an interval of 1 day. In 16 pts a LAA thrombus was detected using TEE,42 pts had SEC/Sludge but no solid thrombus. An LAA thrombus in the CT was described in 26 pts (10%), 6% couldn't definitively diagnose thrombi due to contrast recesses/flow phenomena in 16 pts. In 8 out of 34 events (23%) TEE and CT agreed on the diagnosis of a thrombus, in 6 cases during same-day examinations. 18 pts: LAA thrombus on CT, not on TEE (mean interval: 2d). 8 pts: LAA thrombus on TEE, not on CT (mean interval: 1.5d). In 71% (200 out of 283) of cases, CT and TEE agreed in ruling out a thrombus (p=0.358). LAA flow velocity and thrombus verification by TEE showed a significant correlation (p &amp;lt; 0.001). No correlation was found between the presence of a thrombus on CT and LA volume (p= 0.964). Discussion In 12% of the patients, all treated with OAC, a thrombus was described in at least one of the examinations or in both. Only in one out of four pts TEE and CT agreed on the diagnosis of a thrombus. It was notable that both examinations excluded thrombi in 70%. LAA flow velocity and thrombus verification in the TEE are significant correlated. LA volume and thrombus notification in CT are not related. Conclusion Routine diagnosis of LAA thrombus remains challenging, with frequent discrepancies between TEE, the gold standard, and CT. TEE results depend on the examining physician, while CT is limited by flow phenomena and scan timing.

Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Proteomic biomarkers for noninvasive left atrial appendage thrombus prediction in patients with atrial fibrillation

Introduction and objectivesThe CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment. MethodsDeep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification. ResultsThe LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices. ConclusionsProtein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.

Safety and efficacy of the second-generation cryoballoon for left atrial appendage electrical isolation in canines.

Left atrial appendage electrical isolation (LAAEI) has demonstrated a significant enhancement in the success rate of atrial fibrillation (AF) ablation. Nevertheless, concerns persist about the safety of LAAEI, particularly regarding alterations in left atrial appendage (LAA) flow velocity and the potential risks of thrombus. This study aimed to assess the efficacy and safety of LAAEI, investigating changes in LAA flow velocity in canines. The study comprised a total of 10 canines. The LAAEI procedure used by a 23 mm cryoballoon of the second generation was conducted at least 180 s. Intracardiac ultrasonography (ICE) was employed to quantify the velocity flow of the LAA both prior to and following LAAEI. Following a 3-month period, subsequent evaluations were performed to assess the LAA velocity flow and the potential reconnection. Histopathological examination was conducted. Left atrial appendage electrical isolation was effectively accomplished in all canines, resulting in a 100% acute success rate (10/10). The flow velocity in the LAA showed a notable reduction during LAAEI as compared with the values before the ablation procedure (53.12 ± 5.89 vs. 42.01 ± 9.22 cm/s, P = 0.007). After the follow-up, reconnection was observed in four canines, leading to a success rate of LAAEI of 60% (6/10). The flow velocity in the LAA was consistently lower (53.12 ± 5.89 vs. 44.33 ± 10.49 cm/s, P = 0.006), and no blood clot development was observed. The histopathological study indicated that there was consistent and complete injury to the LAA, affecting all layers of its wall. The injured tissue was subsequently replaced by fibrous tissue. The feasibility of using cryoballoon ablation for LAAEI was confirmed in canines, leading to a significant reduction of LAA flow velocity after ablation. Some restoration of LAA flow velocity after ablation may be linked to the passive movement of the LAA and potential reconnecting. However, this conclusion is limited to animal study; more clinical data are needed to further illustrate the safety and accessibility of LAAEI in humans.

Association of Left Atrial Appendage Morphology and Function With Stroke and Transient Ischemic Attack in Atrial Fibrillation Patients

We aimed to correlate left atrial appendage (LAA) structure and function with the history of stroke/transient ischemic attack (TIA) in patients with atrial fibrillation (AF). We analyzed data of 649 patients with AF who were scheduled for catheter ablation. Patients underwent cardiac CT and transesophageal echocardiography prior to ablation. LAA morphologies depicted by cardiac CT were categorized into four groups: cauliflower, chicken wing, swan and windsock shapes. Mean age was 61.3±10.5 years, 33.9% were female. Prevalence of stroke/TIA was 7.1%. After adjustment for the main risk factors, LAA flow velocity ≤35.3 cm/sec (OR=2.18; 95%CI=1.09-4.61; p=0.033) and swan LAA shape (OR=2.69; 95%CI=0.96-6.86; p=0.047) independently associated with higher risk of stroke/TIA, while windsock LAA morphology proved to be protective (OR=0.32; 95%CI=0.12-0.77; p=0.017) as compared to cauliflower LAA shape. When comparing the differences between LAA morphology groups, we measured significantly smaller LAA orifice area (389.3±137.7 mm2 in windsock vs 428.3±158.9 ml in cauliflower, p=0.021) and LAA volume (7.4±3.0 mm2 in windsock vs 8.5±4.8 mm2 in cauliflower, p=0.012) in patients with windsock LAA morphology, while LAA flow velocity did not differ significantly. Reduced LAA function and swan LAA morphology were independently associated with higher prevalence of stroke/TIA, while windsock LAA shape proved to be protective. When comparing the differences between the various LAA morphology types, significantly lower LAA volume and LAA orifice area were measured in windsock LAA shape as compared to cauliflower LAA shape.

Associations of the left atrial epicardial fat thickness with the thrombosis prevalence and left atrial appendage flow velocity in patients with persistent non-valvular atrial fibrillation

Aim. To study the associations of the left atrial epicardial fat (LAEF) thickness with the thrombosis prevalence and left atrial appendage (LAA) flow velocity in patients with persistent non-valvular atrial fibrillation (AF).Material and methods. Transesophageal echocardiography in 475 patients with persistent non-valvular AF (men 58,9%, age 64,0 (58,3-70,0) years) assessed LAA flow velocity, interatrial septum and left lateral ridge thickness. Their average thickness was used to estimate the LAEF volume.Results. LAA thrombus was detected in 42 (8,8%) patients. LAA flow velocity without thrombus was 32,0 (26,0-39,0) cm/s, with thrombus — 20,0 (14,0-25,8) cm/s (p&lt;0,0001). Depending on the LAEF thickness, patients were divided into 3 tertile groups: group 1 (n=168) — 5,6-7,4 mm, group 2 (n=154) — 7,45-8,2 mm, group 3 (n=153) — 8,25-10,9 mm. In group 1, no thrombus was detected, in group 2, thrombus was detected in 2 (1,3%) patients, in group 3 — in 40 (26,0%) patients (p&lt;0,0001). In the absence of LAA thrombus, flow velocity in the selected groups did not differ (32,0 (26,0-39,0) cm/s, 31,0 (26,0-7,8) cm/s and 31,5 (25,0-40,0) cm/s, (p=0,9514)).Conclusion. EFL thickness, calculated as the average of interatrial septum and left lateral ridge thickness, can be used to study the relationship between epicardial obesity and LAA thrombosis in patients with AF. In patients with persistent non-valvular AF with a LAEF thickness &gt;8,2 mm, LAA thrombosis occurs more than 40 times more often than in patients with a lower LAEF thickness. The influence of LAEF thickness on LAA flow velocity was not revealed in the pre­sent study.

Impact of left atrial appendage thrombus location on diagnostic accuracy of cardiac CT: a single-centre case-control study

ObjectiveCardiac CT (CCT) is an emerging non-invasive modality for assessing left atrial appendage (LAA) thrombus, but the results were conflicting. Our study aims to evaluate the accuracy of CCT for...

Efficacy of Low-Dose Isoproterenol Infusion for the Exclusion of a Left Atrial Appendage Thrombus in Patients With Dense Spontaneous Echo Contrast Caused by Atrial Fibrillation.

In patients with atrial fibrillation (AF) and severe blood stasis in the left atrial appendage (LAA), dense spontaneous echo contrast (SEC) disturbs the distinct visualization of the LAA interior, thus making thrombus diagnosis inconclusive. We aimed to prospectively assess the efficacy and safety of a protocol for a low-dose isoproterenol (ISP) infusion to reduce SEC to exclude an LAA thrombus.Methods and Results: We enrolled 17 patients with AF and dense SEC (Grade 4 or sludge). ISP was infused with gradually increasing doses of 0.01, 0.02, and 0.03 μg/kg/min at 3-min intervals. After increasing the dose to 0.03 μg/kg/min for 3 min, or when the LAA interior was visible, the infusion was terminated. We reassessed the SEC grade, presence of an LAA thrombus, LAA function, and left ventricular ejection fraction (LVEF) within 1 min of ISP termination. Compared with baseline, ISP significantly increased LAA flow velocity, the LAA emptying fraction, LAA wall velocities, and LVEF (all P<0.01). ISP administration significantly reduced the SEC grade (median) from 4 to 1 (P<0.001). The SEC grade decreased to ≤2 in 15 (88%) patients, and the LAA thrombus was excluded. There were no adverse events. Low-dose ISP infusion may be effective and safe to reduce SEC and exclude an LAA thrombus by improving LAA function and LVEF.

Effect of epigenetic regulation on left atrial function and recurrence after catheter ablation in patients with atrial fibrillation

Abstract Background Genetic variation and modifiable risk factors play a significant role in the pathogenesis of atrial fibrillation (AF). However, the influence of epigenetic modification on AF remains to be elucidated. Methods Epigenetic evaluation was performed in 115 AF patients who underwent radiofrequency catheter ablation (RFCA) in a single institution. We measured methylation at approximately 850,000 bp cytosine-phosphate-guanine (CpG) sites in the 115 samples. Results The degree of methylation was compared across seven classification criteria: type of AF, late recurrence, impaired left atrium (LA) function, late gadolinium enhancement, LA diameter, LA volume, and flow velocity of the LA appendage. The four most significantly methylated genes in our cohort were DEFB104B, C3, TANC1, and TMEM9B. The DEFB104B gene (cg20223677 in the transcription start site), which encodes β-defensin 104B, was hypomethylated in three groups: those with late recurrence, impaired LA function, and impaired LAA flow velocity. Enriched functional annotation of the differentially methylated datasets revealed that five out of the seven AF groups in this cohort were associated with genes involved in the cell movement of endothelial cell lines, sprouting angiogenesis by endothelial cell lines, or migration of endothelial cell lines. Conclusion In this study, epigenetic profiling revealed that epigenetic modification might affect crucial traits of AF, such as the degree of atrial myopathy and treatment effects after RFCA, suggesting the hypothesis that the pathogenesis of AF might be affected by not only genetic variation or modifiable factors but also by epigenetic modulation. The identified methylation-susceptible loci can be used in targeting for epigenetic-based therapeutic agents.

Предиктори утримання синусового ритму в пацієнтів із пізньою персистентною фібриляцією передсердь після електричної кардіоверсії під час 6-місячного проспективного спостереження

The aim – to study the predictors of sinus rhythm (SR) maintenance in patients with persistent atrial fibrillation (AF) and duration of AF episode ≥90 days at 6-months follow-up after elective direct current (DC) cardioversion.Materials and methods. The cohort single-center study analyzed clinical and instrumental data from 59 persistent AF patients with duration of its episode ≥90 days (up to 12 months), who underwent an elective DC cardioversion. At 6-months follow-up, patients were subdivided into the groups depending on SR maintenance: 32 (54 %) patients with a maintained SR (G1), and 27 (46 %) patients with a failure to maintain SR (G2).Results. G2, as compared to G1, demonstrated more advanced heart failure (stage C occurred in 74 % and 44 %, respectively [p=0,019]). According to transthoracic echocardiography (TTE) data, G1, as opposed to G2, was characterized by better baseline structure parameters of left heart chambers, particularly the diameter of left atrium (LA), end-diastolic and end-systolic volumes left ventricular (LV) volumes, higher LV systolic function (by LV ejection fraction [EF]), and the majority of the cases without or with mild pulmonary hypertension (PH). Transesophageal echocardiography data suggested the cases of LA spontaneous (echo) contrast and LA appendage flow velocity (LAAFV) ≤ 40 cm/s to be more frequent in G2, in contrast to G1. We revealed the following predictors of SR maintenance after DC cardioversion at 6-months follow-up: higher LV EF (OR 1,07 (95 % CI 1,01–1,13); р=0,021); LAAFV &gt; 40 cm/s (OR 4,33 (95 % CI 1,06–17,78); р=0,042), and less advanced PH (OR 0,24 (95 % CI 0,06–0,93); р=0,038). TTE data from G1 at 6-months follow-up after DC cardioversion suggested the reverse remodeling of both atria (the decrease of LA diameter, LA and right atrium volumes and their indexes). Additionally, G2 demonstrated a worsening in LV systolic function (the rise of LV end-systolic volume and decrease of LV EF), as opposed to G1. Moreover, at 6-months follow-up, G2 patients presented with more advanced severity of PH, as well as mitral and tricuspid regurgitation, in contrast to G1.Conclusions. Better LV systolic function, LAAFV &gt; 40 cm/s and less advanced PH were the predictors of SR maintenance in patients with persistent AF and duration of its episode ≥ 90 days at 6-months follow-up after elective DC cardioversion. The SR maintenance at 6-months follow-up associated with the reverse remodeling of let heart chambers and right atrium. On the contrary, a failure to maintain SR associated with the decrease of LV systolic function, and more advanced PH, mitral and tricuspid regurgitation.