Paroxysmal Atrial Fibrillation Group Research Articles

The Role of Galectin-3 Levels for Predicting Paroxysmal Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source.

Background/Objectives: Paroxysmal atrial fibrillation (PAF) is an important cause that is thought main potential factor in Embolic stroke of undetermined source (ESUS). Extended Holter ECG is an expensive and time-consuming examination. It needs another tools for predicting PAF in ESUS patients. In this study, serum galectin-3 levels, ECG parameters (PR interval, P wave time and P wave peak time) LA volume index, LA global peak strain and atrial electromechanical conduction time values were investigated for predicting PAF. Methods: 150 patients with ESUS and 30 volunteers for the control group were recruited to study. 48-72 h Holter ECG monitoring was used for detecting PAF. Patients were divided into two groups (ESUS + PAF and ESUS-PAF) according to the development of PAF in Holter ECG monitoring. Results: 30 patients with ESUS whose Holter ECG monitoring showed PAF, were recruited to the ESUS + PAF group. Other 120 patients with ESUS were recruited to the ESUS-PAF group. PA lateral, PA septum, and PA tricuspid were higher in the ESUS + PAF group (p < 0.001 for all). Serum galectin-3 levels were significantly higher in ESUS + PAF than in ESUS-PAF and control groups (479.0 pg/mL ± 435.8 pg/mL, 297.8 pg/mL ± 280.3 pg/mL, and 125.4 ± 87.0 pg/mL, p < 0.001, respectively). Serum galectin-3 levels were significantly correlated with LAVI, PA lateral, and global peak LA strain (r = 0.246, p = 0.001, p = 0.158, p = 0.035, r = -0.176, p = 0.018, respectively). Conclusion: Serum galectin-3 levels is found higher in ESUS patients which developed PAF and Serum galectin-3 levels are associated LA adverse remodeling in patients with ESUS.

Impact of pulmonary vein variant anatomy during cryo-ablation in paroxysmal and persistent AF patients: 1-year outcome from a nationwide multicenter clinical setting

Abstract Background Complete electrical pulmonary vein isolation (PVI) by cryo-balloon approach is a well-established ablation strategy of atrial fibrillation (AF). While contrast findings exist regarding the influence of variant pulmonary vein (PV) anatomy on predicting AF recurrence, limited data are currently available specifically for cases involving the POLARx cryoablation system during PVI. Purpose We report the real-world experience of POLARx in the context of de novo AF ablation in a multicenter Italian registry. Methods Consecutive patients undergoing AF ablation from the CHARISMA registry at 10 Italian centres were included. Protocol-directed cryoablation was delivered for 180 sec or 240 sec according to operator’s preference for isolation achieved in ≤60 sec, or 240 sec if isolation occurred &amp;gt;60 sec or when time to isolation was not available. The ablation endpoint was PVI as assessed by entrance and exit block. All patients were followed-up for at least 12 months after the procedure. Results Four-hundred twenty-nine patients were included (n=358, 83.4% paroxysmal AF, n=71, 16.6% persistent AF, mean age 60.7±10 years, 28.3% female, mean LVEF 58±8%). PVI was achieved in all pts using only cryoablation. Twenty-eight (6.6%) patients exhibited an anatomical variant: 17 (4.0%) a common ostium and 11 (2.6%) an adjunctive PV. The mean number of freeze applications per patient was 5.1 (1.2 for LSPV, 1.3 for LIPV, 1.2 for RSPV and 1.3 for RIPV). Over a median of 398[370-461] days of follow-up, 14 (3.2%) patients experienced an early recurrence of AF during the 90-day blanking period. Overall, 63 patients (14.7%) suffered an AF recurrence after the 90-day blanking period (median time to recurrence 342[171-381] days). The proportion of patients exhibiting AF/AT recurrences was higher in the persistent AF group (17 out 71, 23.9%) than in the paroxysmal AF group (46 out 358, 12.8%, p=0.026), with a hazard ratio of 2.02 (95%CI: 1.2 to 3.5, p=0.0137) whereas patients with anatomy variant showed a similar AF/AT recurrence rate (5 out 28, 17.9%) than in the standard anatomy group (58 out of 401, 14.5%) with a hazard ratio of 1.43 (0.6 to 3.6, p=0.441). Four (0.9%) transient phrenic nerve palsy were observed, both with full recovery in the 48-h post procedure; no major procedure-related adverse events were reported. Conclusion In this multicenter study, the cryo-balloon system demonstrated safety and efficacy in treating both paroxysmal and persistent AF patients, yielding a low incidence of AF/AT recurrence during follow-up, regardless of the presence of variant PV anatomy.

The effects of radiofrequency catheter ablation for atrial fibrillation on right ventricular function

Abstract Background The effects of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) on right ventricular (RV) function are not well known. Methods Patients who underwent RFCA for AF and underwent pre- and post-procedural echocardiography were enrolled. Fractional area change (FAC), RV free-wall longitudinal strain (RVFWSL), and RV 4-chamber strain (RV4CSL) were measured. Changes in FAC, RVFWSL, and RV4CSL before and after RFCA were compared among paroxysmal (PAF), persistent (PeAF), and long-standing persistent AF (LSPeAF) groups. Results A total of 164 participants (74 PAF, 47 PeAF, and 43 LSPeAF; age, 60.8±9.8 years; men, 74.4%) was enrolled. The patients with PeAF and LSPeAF had worse RV4CSL (p&amp;lt;0.001) and RVFWSL (p&amp;lt;0.001) than those with PAF and reference values. Improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared with the PAF and LSPeAF groups (ΔRV4CSL, 8.4% [5.1–11.6] in PeAF vs. 1.0% [-1.0–4.1] in PAF, 1.9% [-0.2–4.4] in LSPeAF, p&amp;lt;0.001; ΔRVFWSL, 9.0% [6.9–11.5] in PeAF vs. 0.9% [-1.4–4.9] in PAF, 1.0% [-1.0–3.6] in LSPeAF, p&amp;lt;0.001). Conclusions RV function is impaired in patients with PeAF and LSPeAF than in those with PAF. RV function is more improved after RFCA in patients with PeAF than in those with PAF or LSPeAF.Changes of echocardiographic parameters

Left atrial appendage closure outcomes in relation to atrial fibrillation patterns: a comprehensive analysis.

The effect of atrial fibrillation (AF) patterns on outcomes remains controversial. This study aims to evaluate the influence of AF type on the risk of cardiocerebrovascular events after left atrial appendage closure (LAAC) at long-term follow-up. AF was categorized as paroxysmal AF (PAF) and non-PAF (NPAF). The baseline characteristics, procedural data, peri-procedural complications, and long-term outcomes between patients with PAF and NPAF after LAAC were compared. We analyzed 410 AF patients (mean age 74.8 ± 8.2 years; 271 male; 144 with PAF, 266 NPAF). The NPAF group tended to be older (≥75 years), male, and have chronic kidney disease (CKD) compared with the PAF group. The procedural data and peri-procedural complications were comparable. During 2.2 ± 1.5 years of follow-up, the incidences of thromboembolism, major bleeding, and device-related thrombus (DRT) did not differ between the two groups. The observed risk of thromboembolism and major bleeding was significantly lower than the estimated risk based on the CHA2DS2-VASc and HAS-BLED scores, respectively, in patients who underwent LAAC, regardless of the AF type. NPAF patients were associated with a higher risk of all-cause mortality, non-cardiovascular mortality, and combined efficacy endpoints. This association disappeared after propensity score matching (PSM) analysis. The risk of thromboembolism and major bleeding was lower in patients who underwent LAAC, regardless of the AF type. Although NPAF often coexists with multiple risk factors, it was not associated with worse long-term outcomes after LAAC when compared with PAF.

Metformin reduces new-onset atrial fibrillation risk rather than atrial fibrillation burden in type 2 diabetes patients: A case-control study

BackgroundThe effects of metformin on atrial fibrillation (AF) in type 2 diabetes patients remain unclear. We aimed to explore the effects of metformin on AF, including new-onset AF and AF burden, in type 2 diabetes patients with pacemakers. Methods and resultsThis retrospective study included a total of 227 patients. Based on the presence of paroxysmal AF, the patients were divided into a paroxysmal AF group (n = 80) and a non-AF group (n = 147). In the non-AF group, a significant association was observed between metformin use and a lower risk of new-onset AF in multivariable Cox hazards models (hazard ratio [HR]: 0.36; 95 % confidence interval [CI]: 0.14–0.91; p = 0.0311*) when adjusted for age, sex, body mass index (BMI), drinking, smoking, left atrial dimension, creatinine, complications, and drugs. In the paroxysmal AF group, univariable analysis indicated no association between the AF burden and metformin use (p = 0.817). Furthermore, when adjusted for metformin use, age, sex, BMI, drinking, smoking, cardiovascular disease, myocardial infarction, heart failure, stroke, and ejection fraction in multivariable Cox hazards models, we found a lower proportion of major adverse cardiovascular events (MACEs) both in the total (HR: 0.28; 95 % CI: 0.1–0.82; p = 0.0202*) and the non-AF group (HR: 0.19; 95 % CI: 0.05–0.79; p = 0.0223*) compared to that in the AF group (HR: 0.31; 95 % CI: 0.02–4.41; p = 0.3879). ConclusionIn type 2 diabetes patients with pacemakers, metformin reduced the probability of new-onset AF instead of addressing the AF burden. Furthermore, metformin therapy decreased the incidence of MACEs in type 2 diabetes patients without AF.

The Effects of Radiofrequency Catheter Ablation for Atrial Fibrillation on Right Ventricular Function.

The effects of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) on right ventricular (RV) function are not well known. Patients who underwent RFCA for AF and underwent pre- and post-procedural echocardiography were enrolled consecutively. Fractional area change (FAC), RV free-wall longitudinal strain (RVFWSL), and RV 4-chamber strain including the ventricular septum (RV4CSL) were measured. Changes in FAC, RVFWSL, and RV4CSL before and after RFCA were compared among paroxysmal AF (PAF), persistent AF (PeAF), and long-standing persistent AF (LSPeAF) groups. A total of 164 participants (74 PAF, 47 PeAF, and 43 LSPeAF; age, 60.8 ± 9.8 years; men, 74.4%) was enrolled. The patients with PeAF and LSPeAF had worse RV4CSL (p<0.001) and RVFWSL (p<0.001) than those with PAF and reference values. Improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared with the PAF and LSPeAF groups (ΔRV4CSL, 8.4% [5.1, 11.6] in PeAF vs. 1.0% [-1.0, 4.1] in PAF, 1.9% [-0.2, 4.4] in LSPeAF, p<0.001; ΔRVFWSL, 9.0% [6.9, 11.5] in PeAF vs. 0.9% [-1.4, 4.9] in PAF, 1.0% [-1.0, 3.6] in LSPeAF, p<0.001). In patients without recurrence, improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared to the LSPeAF group. RV systolic function is more impaired in patients with PeAF and LSPeAF than in those with PAF. RV systolic function is more improved after RFCA in patients with PeAF than in those with PAF or LSPeAF.

Evaluation of an Optimized Workflow for the Radiofrequency Catheter Ablation of Paroxysmal Atrial Fibrillation.

BACKGROUND A significant number of atrial fibrillation (AF) recurrences occur after initial ablation, often due to pulmonary vein reconnections or triggers from non-pulmonary veins. MATERIAL AND METHODS Patients with paroxysmal AF who underwent radiofrequency catheter ablation for the first time were enrolled. Base on propensity score matching (1: 1 matching), 118 patients were selected for an optimized workflow for the radiofrequency catheter ablation of paroxysmal AF (OWCA) group and a conventional group. Comparative analysis of the acute and 12-month clinical outcomes was conducted. Moreover, an artificial intelligence analytics platform was used to evaluate the quality of pulmonary vein isolation (PVI) circles. RESULTS PVI was successfully achieved in all patients. Incidence of first-pass isolation of bilateral PVI circles was higher (P=0.009) and acute pulmonary vein reconnections was lower (P=0.027) in the OWCA group than conventional group. The OWCA group displayed a significant reduction in the number of fractured points (P<0.001), stacked points (P=0.003), and a greater proportion of cases in which the radiofrequency index achieved the target value (P=0.003). Additionally, the contact force consistently met the force over time criteria (P<0.001) for bilateral PVI circles in the OWCA group, accompanied by a shorter operation time (P=0.017). During the 12-month follow-up period, the OWCA group exhibited a higher atrial arrhythmia-free survival rate following the initial ablation procedure than did the conventional group. CONCLUSIONS The optimized workflow for radiofrequency catheter ablation of paroxysmal AF could play a crucial role in creating higher quality PVI circles. This improvement is reflected in a significantly elevated 12-month atrial arrhythmia-free survival rate.

Quantitative assessment of left ventricular myocardial work in patients with different types of atrial fibrillation by non-invasive pressure-strain loop technique.

This study aimed to analyze myocardial work in patients with atrial fibrillation (AF) using a noninvasive pressure strain loop (PSL) technique to provide a basis for the quantitative assessment of left ventricular (LV) systolic function. LV myocardial work of 107 AF patients (56 with paroxysmal atrial fibrillation and 51 with persistent atrial fibrillation) and 55 healthy individuals were assessed by the noninvasive PSL and then compared. Global longitudinal strain (GLS) in absolute values, global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the AF group than control group, whereas peak strain dispersion (PSD) and global wasted work (GWW) were significantly higher (P<.05). Further subdivision according to the AF type revealed that, compared with the controls, GLS in absolute values and GWE decreased significantly; PSD and GWW increased significantly in the paroxysmal AF group (P<.05). Nevertheless, GWI and GCW were not significantly different between paroxysmal AF and control groups (P>.05). Compared to paroxysmal AF, persistent AF induced a further decrease in absolute GLS and GWE and a further increase in GWW (P<.05), but PSD did not increase further (P>.05). Multiple linear regression analysis showed that GWI and GCW were independently associated with systolic blood pressure. GWW was associated with types of AF and left atrial volume index (LAVI). GWE was correlated with age, types of AF, disease duration, and LAVI. Receiver operating characteristic curve analysis showed that the area under the curve predicting myocardial injury was higher for GWE and GWW than for GLS (area under the curve: .880, .846, and .821, respectively). Non-invasive PSL can quantitatively assess LV systolic function in patients with different kinds of AF and detect early subclinical myocardial injury in patients with paroxysmal AF. GWE and GWW outperform GLS and LV ejection fraction when assessing myocardial injury. Systolic blood pressure, type of AF, LVAI, disease duration, and age may be associated with myocardial injury in patients with AF.

Clinical Utility of Baseline Brain Natriuretic Peptide Levels on Health Status Outcomes after Catheter Ablation for Atrial Fibrillation in Individuals without Heart Failure.

Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in a broader range of patients. Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g., documented history of HF, left ventricular ejection fraction ≤ 40%, or BNP levels ≥ 100 pg/mL). Participants, aged 61 ± 10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year. A lower baseline BNP correlated with reduced AFEQT scores. Post CA, all groups showed significant AFEQT score improvements. The lower-BNP group displayed notable enhancements (18.2 ± 1.2, 15.0 ± 1.1, 12.6 ± 1.2, 13.6 ± 1.2, p < 0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/mL) exhibited significant QOL improvements. Comparing paroxysmal AF (PAF) and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements. This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvements.

Association of Atrial Fibrillation Progression With Left Atrial Functional Reserve and Its Reversibility.

Atrial fibrillation (AF) progression is closely related to heart failure occurrence, and catheter ablation carries a beneficial effect for heart failure prevention. Recently, particular attention has been given to left atrial (LA) function and functional reserve in the pathogenesis linking AF and heart failure, although its significance and reversibility is not well studied. We prospectively investigated 164 patients with AF with normal left ventricular systolic function and free from heart failure who underwent first catheter ablation and pre-/postprocedural echocardiography. Conventional and speckle-tracking echocardiography were performed at rest and during passive leg lifting to assess LA size, LA reservoir strain (LARS), and functional reserve calculated as passive leg lifting-LARS - rest-LARS. Patients were categorized into 3 AF subtypes: paroxysmal AF (N=95), persistent AF (PeAF; N=50), and long-standing persistent AF (LS-PeAF; N=19). The PeAF and LS-PeAF groups had larger LA size and reduced LARS compared with the paroxysmal AF group (all P<0.05). LA functional reserve was significantly impaired in the LS-PeAF group (P=0.003). In multivariable analysis, LS-PeAF and advanced age were significantly associated with impaired LA functional reserve. Among 149 patients with sinus rhythm 1 to 2 days after catheter ablation, LARS was significantly improved in both PeAF and LS-PeAF groups but was still lower than that in the paroxysmal AF group. Sinus rhythm restoration also led to amelioration of LA functional reserve in patients with LS-PeAF. AF progression was related to impaired LARS and LA functional reserve, and restoration of sinus rhythm might contribute to early LA reverse remodeling.

The value of serial echocardiography in risk assessment of patients with paroxysmal atrial fibrillation.

Progression from paroxysmal to persistent atrial fibrillation (AF) is associated with increased morbidity and mortality. We examined the association of left atrial (LA) remodeling by serial echocardiography, and AF progression over an extended follow-up period. Two-hundred ninety patients (mean age 61 ± 11years, 73% male) who underwent transthoracic echocardiography performed at first presentation for non-valvular paroxysmal AF (PAF) and repeat echocardiogram 1-year later, were followed for progression to persistent AF. LA and left ventricular (LV) dimensions, volumes, LA reservoir, conduit and booster pump strains, LV global longitudinal systolic strain (GLS) assessedby 2D speckle tracking, and PA-TDI (time delay between electrical and mechanical LA activation- reflecting the extent of LA fibrosis) were compared on serial echocardiography. Sixty-nine (24%) patients developed persistent AF over a mean follow-up period of 6.3years. At baseline, patients with subsequent persistent AF had larger LA dimensions (46mm vs. 42mm, p < 0.001), indexed LA volumes (41ml/m2 vs. 34ml/m2, p < 0.001), lower LA reservoir and conduit strain (17.6% vs. 27.6%, p < 0.001; 10.5% vs. 16.3%, p < 0.001; respectively) and longer PA-TDI (155ms vs. 132ms, p < 0.001) compared to the PAF group. Patients with subsequent persistent AF showed over time significant enlargement in LA volumes (from 37.7ml/m2 to 42.4ml/m2, p < 0.001), lengthening of PA-TDI (from 142.2ms to 162.2ms, p = 0.002), and decline in LA reservoir function (from 21.9% to 18.1%, p = 0.024) after adjusting for age, gender, diabetes and LV GLS. There were no changes in LA diameter, LA conduit or booster pump function. Conversely, the PAF group showed no decline in LA function. Patients who developed persistent AF had larger LAsize and impaired LA function and atrial conduction times at baseline, compared to patients who remained PAF. Over the 1-year time course of serial echocardiographic evaluation, there was progression of LA remodeling in patients who subsequently developed persistent AF, but not in patients who remained inPAF.

The Correlation of Inflammation, Oxidative Stress, and Hippocampal Perfusion in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is closely related to abnormal cerebral blood flow. Inflammation and oxidative stress have always been important factors in the pathophysiology of AF. It remains unknown whether inflammation and oxidative stress are correlated to hippocampal perfusion in patients with AF.Sixty-three patients with AF with normal hippocampal blood perfusion (NHBP) were compared to 71 patients with AF with abnormal hippocampal blood perfusion (AHBP) using a case-control study design. The serum levels of inflammation and oxidative stress were measured. The hippocampal perfusion was detected. (1) The serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and oxidized low-density lipoprotein (ox-LDL) were statistically higher in the AHBP group than in the NHBP group. In the AHBP subgroup analysis, the serum levels of hs-CRP and IL-6 were statistically higher in patients with persistent AF than those with paroxysmal AF. (2) The relative cerebral blood volume (rCBV), mean transit time (MTT), and the time-to-peak (TTP) were statistically higher in the AHBP group than in the NHBP group. Moreover, cerebral blood flow (rCBF) was statistically lower in the AHBP group than in the NHBP group. (3) relative cerebral blood volume (rCBV), rCBF, MTT, and TTP were passively associated with serum hs-CRP and IL-6; rCBV, rCBF, and MTT were positively associated with ox-LDL. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF after multivariate logistic regression analysis.Oxidative stress and inflammatory biomarkers were increased in patients with AF with AHBP, in which the serum levels of hs-CRP and IL-6 in the persistent AF group were statistically higher than those in the paroxysmal AF group. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF.

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&amp;lt;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&amp;lt;0.001, p=0.003, and p&amp;lt;0.001, respectively). AngII infusion reduced the number of LYVE1-positive atrial LECs (p&amp;lt;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.

Left atrial dysfunction during stress in patients with atrial fibrillation

Abstract Background Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS). Objective This study sought to assess LA function at rest and during stress across the spectrum of AF. Methods In a prospective, multicentric, observational study design, we studied a cohort of 2391 patients (age=67±12 years; 1459, 61% male): 2142 (89.6%) were in sinus rhythm (SR, Group 1), 165 (6.9%) had a history of paroxysmal AF (Group 2) and 84 (3.5%) were in permanent AF (Group 3). All patients were referred for CCS and underwent stress echocardiography (SE) with exercise (n=1092, 45.3%), dobutamine (n=320, 13.4%) or vasodilators (n= 989, 40.3%: dipyridamole n=963 and adenosine n=26). Left atrial volume index (LAVI) and LA reservoir strain (LASr) were assessed at rest and peak stress. Analysis with different vendors was performed offline on anonymized cine-loops by observers unaware of the study hypothesis. Results The progressive increase in LA dysfunction from Group 1 to 3 was accompanied by greater signs of pulmonary congestion and LV dysfunction (see Table 1). In particular, LASr progressively decreased from Group 1 to 3, both at rest and during stress, regardless of the stress employed (see Figure 1). Conclusions LA reservoir function can be easily assessed with deformation imaging at rest and during exercise or pharmacological stress echocardiography. LA dysfunction progressively increases from SR to paroxysmal to permanent AF and is associated with more important LV systolic dysfunction, LV filling pressure, and pulmonary congestion in CCS.Table 1.Echocardiographic parametersFigure 1.LAVI and LASr at rest and peak

The exploratory clinical trial of AI-enabled Holter electrocardiogram for diagnosis of paroxysmal atrial fibrillation from sinus rhythm waveforms

Abstract Backgrounds Machine learning (ML) models using convolutional neural networks (CNNs) have been successfully applied to arrhythmia detection and prediction. The current study aimed to develop a CNN-based AI algorithm for the prediction of paroxysmal atrial fibrillation (PAF) patients during sinus rhythm waveforms from Holter electrocardiograms. Methods A ML model was developed by using 2-leads from Holter ECG waveforms divided into slots of 30 seconds each. As training data, we prepared &amp;gt; 300000 slots with sinus rhythm and they were subsequently converted to image data for application to the CNN-based AF detection algorithm. The performance metrics obtained for the ML model for PAF detection were as follows: sensitivity, 85.2 %; specificity, 64.0 % and AUC for PAF prediction was 0.84. To validate the performance of the ML model, multicenter clinical trial was conducted. The clinical trial was conducted at three independent centers and included 24 patients with PAF and 20 patients in true sinus rhythm. Five factors were matched between the PAF and sinus groups: age, gender, hypertension under treatment, diabetes under treatment, and smoking. Waveform data from validation datasets to Grad-CAM were applied to obtain explainable AI (XAI) images, which allowed for a heat map over the waveform to be produced. Results For the primary endpoint, the estimated sensitivity and specificity [95% CI] were 91.7% [73.0-99.0%] and 65.0% [40.8-84.6%], respectively (Table 1). The sensitivity and specificity of the secondary endpoints using 10 time-independent slots were the same as for the primary endpoint. Regarding safety endpoints, no adverse events attributable to the test device itself were observed. Based on the regions of interest highlighted via Grad-CAM, the most contributing featured regions to predict PAF were indicated by areas on P waves and QT area (Figure 1). Featured regions to rule out the existence of PAF indicated areas just on QRS waves were also present. It was therefore determined that the proposed CNN-based ML model focuses on the P-wave area and atrial repolarization area in the case of PAF. Conclusion The study suggested that 2-lead Holter ECG with 30 second slot could detect PAF patients from their sinus rhythm waveforms and the performance was more effectively than using 12-lead ECGs. The results of this clinical trial are expected to contribute to the screening of patients with PAF that could not be detected by a single time Holter ECG.Table 1Figure 1

Elevated liver fibrosis-4 index predicts recurrence after catheter ablation for atrial fibrillation in patients with heart failure.

The fibrosis-4 (FIB-4) index is a noninvasive scoring system that is used to assess the progression of liver fibrosis. This study aimed to assess whether the FIB-4 index is associated with recurrent atrial fibrillation (AF) after catheter ablation in patients with and without heart failure (HF). We included 1,184 patients who underwent initial AF catheter ablation between 2016 and 2021. The patients were classified into low-risk (< 1.3), intermediate-risk (1.3-2.67), and high-risk (> 2.67) groups based on their FIB-4 indices at baseline. The patients were divided into HF (n = 552) and non-HF groups (n = 632); the HF group was further divided into paroxysmal AF (PAF) and non-PAF groups. AF recurrence after catheter ablation was then compared among the groups. In the non-HF group, no significant differences in recurrence after ablation were observed between the low-(n = 219), intermediate-(n = 364), and high-risk (n = 49) groups. In contrast, in the HF group, the intermediate-(n = 341) and high-risk (n = 112) groups had significantly higher recurrence rates than the low-risk group (n = 99) (log-rank test, p = 0.005). This association remained significant after multivariate analysis (hazard ratio [HR]:1.374; p = 0.027). The FIB-4 index increased incrementally as the brain natriuretic peptide levels and severity of tricuspid regurgitation increased. The FIB-4 index was an independent predictor of recurrence in the non-PAF HF group (HR:1.498; p = 0.007) but not in the PAF group. The FIB-4 index may be a useful predictor of AF recurrence after catheter ablation in patients with HF, particularly in those with non-PAF.

Risk stratification of atrial fibrillation and stroke using single nucleotide polymorphism and circulating biomarkers.

Atrial fibrillation (AF) is the most common sustained arrhythmia, and it causes a high rate of complications such as stroke. It is known that AF begins as paroxysmal form and gradually progresses to persistent form, and sometimes it is difficult to identify paroxysmal AF (PAF) before having stroke. The aim of this study is to evaluate the risk of PAF and stroke using genetic analysis and circulating biomarkers. A total of 600 adult subjects were enrolled (300 from PAF and control groups). Peripheral blood was drawn to identify the genetic variation and biomarkers. Ten single nucleotide polymorphisms (SNPs) were analyzed, and circulating cell-free DNA (cfDNA) was measured from plasma. Four microRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were quantified in serum using quantitative RT-PCR. Genotyping identified 4 single nucleotide polymorphisms (SNPs) that were significantly associated with AF (rs6817105, rs3807989, rs10824026, and rs2106261), and the genetic risk score using 4 SNPs showed the area under the curve (AUC) of 0.631. Circulating miRNAs and cfDNA did not show significant differences between PAF and control groups. The concentration of cfDNA was significantly higher in patients with a history of stroke, and the AUC was 0.950 to estimate the association with stroke. The risk of AF could be assessed by genetic risk score. Furthermore, the risk of stroke might be evaluated by plasma cfDNA level.

Rest and Stress Left Atrial Dysfunction in Patients with Atrial Fibrillation.

Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

Left atrial strain superior to structural remodeling in identifying occult atrial fibrillation.

Occult atrial fibrillation (AF) is a significant risk factor for occult stroke but is difficult to detect. Myocardial strain, based on speckle tracking echocardiography (STE), can detect subclinical changes in left atrial (LA) function. This study aimed to investigate the diagnostic value of LA strain in identifying asymptomatic AF patients with normal electrocardiograms and healthy volunteers. A total of 354 subjects were retrospectively enrolled. Patients were divided into two groups based on whether they had AF during echocardiography. Patients with sinus rhythm during echocardiography were further divided into healthy control group and occult AF group. Patients with AF during echocardiography were further divided into paroxysmal AF group and persistent AF group. LA mechanical function measured by STE was compared between patients with asymptomatic AF and volunteers. Conventional echocardiographic indicators were measured. The diagnostic value of LA strain for identifying asymptomatic AF was assessed by univariate and multivariate regression analysis and receiver operating characteristic (ROC) curves. Occult AF patients had higher NT-proBNP levels, larger RA area, larger LAVmax and decreased LAEF than control group. However, occult AF patients had lower NT-proBNP levels, RA area and LAVmax and higher LAEF than paroxysmal and persistent AF. The measured LA reservoir strain (LASr), LA conduit strain (LAScd), LA contraction strain (LASct) of occult AF group was significantly lower than that of control group. However, occult AF patients had preserved LAScd and LASct than paroxysmal and persistent AF. RA area, LAEF and LASr were remarkable correlation with occult AF after adjustment for NT-proBNP, LAVmax, and LAScd. The area under curve of ROC for LASr was the greatest among RA area, LAEF and LASr, with a cut-off value of 34.1% (sensitivity: 75.4%, specificity: 87.6%). LASr can identify occult AF in the asymptomatic population. Patients with LASr values ≤34.1% have a higher incidence of occult cardiac dysfunction. These findings help identify patients with occult AF and further risk stratification for the AF population.

Circulating Neuropeptide Y May Be a Biomarker for Diagnosing Atrial Fibrillation

Introduction: Sympathetic nervous system disorder promotes atrial fibrillation (AF), and neuropeptide Y (NPY) is an important neurotransmitter. This study aimed to explore the predictive value of plasma NPY in patients with AF. Methods: Five hundred seventy-six patients were divided into AF (including paroxysmal and long-standing persistent AF; 360) and sinus rhythm (SR) groups (216). NPY level was detected using enzyme-linked immunosorbent assay, and NPY mRNA expression level was detected using quantitative polymerase chain reaction. Logistic regression was used to analyse the risk factors for AF; the correlations between blood NPY level and age, body mass index (BMI), left ventricular ejection fraction, left atrial diameter (LAD), and European Heart rate Association (EHRA) score in patients with AF were determined. The receiver operating characteristic (ROC) curve was utilised to predict AF. Results: Plasma NPY levels were found to be higher in patients with AF than in patients with SR and in patients with long-standing persistent AF than in patients with paroxysmal AF; blood NPY mRNA levels were higher in the paroxysmal and long-standing persistent AF groups compared to the SR group (p < 0.05). Increased age {odds ratio (OR) = 1.201 (95% confidence interval [CI]: 1.01, 1.427)} and high NPY [OR = 1.239 (95% CI: 1.022, 1.501)] were factors found to affect AF detrimentally. NPY was associated with BMI (r = 0.5856, p < 0.05), LAD (r = 0.4023, p < 0.05), and EHRA score (r = 0.898, p < 0.05). The ROC curve for the predictive value of plasma NPY levels for AF showed an area under the curve (AUC) value of 0.919 (p < 0.05), while that for long-standing persistent AF showed an AUC of 0.784 (p < 0.05). Conclusion: Circulating NPY may be a promising molecular biomarker of AF.