scholarly journals TGFβ Is Specifically Upregulated on Circulating CD14++ CD16+ and CD14+ CD16++ Monocytes in Patients with Atrial Fibrillation and Severe Atrial Fibrosis

2018 ◽  
Vol 49 (1) ◽  
pp. 226-234 ◽  
Author(s):  
David Heinzmann ◽  
Stefan Fuß ◽  
Saskia v. Ungern-Sternberg ◽  
Jürgen Schreieck ◽  
Meinrad Gawaz ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Sinus Rhythm ◽  
Low Voltage ◽  
Strong Increase ◽  
Atrial Remodeling ◽  
Myocardial Remodeling ◽  
Monocyte Subsets ◽  
Atrial Fibrosis ◽  
Voltage Mapping

Background/Aims: Fibrotic remodeling of the atria plays a key role in the pathogenesis of atrial fibrillation (AF). As little is known about the contribution of circulating monocytes in atrial remodeling and the pathophysiology of AF, we investigated profibrotic factors in different subsets of circulating monocytes obtained from patients with atrial fibrillation undergoing catheter ablation. Methods: A 3D high density voltage mapping was performed in sinus rhythm to evaluate the extent of low-voltage areas (LVAs) in the atria of 71 patients with persistent AF. Low-voltage was defined as signals of < 0.5mV during sinus rhythm. Prior to ablation, blood was drawn and monocytes were analyzed by FACS. Based on the expression of CD14 and CD16, three subgroups including CD14++ CD16- (‘classical’), CD14++ CD16+ (‘intermediate’), and CD14+ CD16++ (‘non-classical’) were analyzed for the expression of TGFb, CD147, and MMP-9, representing pivotal profibrotic pathways in myocardial remodeling. Results: Expression of TGFb was increased in CD14+ monocytes of patients with extensive LVAs compared to patients with a low extend of LVAs. While CD14++ CD16- monocytes showed no difference, CD14++ CD16+ and CD14+ CD16++ monocytes showed a strong increase of TGFb abundance. Although CD147 and MMP-9 are strongly associated with myocardial fibrosis, we found no difference in expression between the two groups in any monocyte subsets. Conclusion: TGFb is specifically upregulated on CD14++ CD16+ and CD14+ CD16++ monocytes in patients with extensive LVAs undergoing catheter ablation.

Abstract 15692: Voltage Mapping in Atrial Fibrillation vs Sinus Rhythm: Results From the Mavs Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Carola Gianni ◽  
Jerri A Cunningham ◽  
Sanghamitra Mohanty ◽  
CHINTAN TRIVEDI ◽  
Domenico G Della Rocca ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Low Voltage ◽  
Lateral Wall ◽  
Posterior Wall ◽  
Anterior Wall ◽  
Inferior Wall ◽  
Voltage Mapping ◽  
First Time ◽  
Mapping Catheter

Background: Left atrial (LA) scar can be identified with bipolar voltage mapping during sinus rhythm (SR). It is not clear whether the same voltage criteria can be applied during atrial fibrillation (AF). Objective: Aim of this study was to compare voltage maps performed in the same patient both in AF and SR. Methods: Voltage mapping was performed using a 10-pole circular mapping catheter in patients with non-paroxysmal AF undergoing first time RF ablation. For descriptive purposes, the LA was divided in 6 regions: septum, posterior wall (PW), inferior wall (IW), lateral wall, anterior wall, and roof. The threshold for low voltage was <0.5 mV (with a color range setting 0.2-0.5 mV). Mild “scar” was defined as an area low voltage 5-20%, moderate 20-35% and severe as >35%. Results: 16 patients (62% persistent AF, 38% longstanding persistent AF) were included in the study. The map density was comparable during AF and SR (mean points per map 551 vs 547, paired t test P = NS). 2 patients displayed normal voltage during both AF and SR. 14 patients showed areas of low voltage during AF, which were still present during SR in 8. All patients with mild “scarring” during AF (n = 4), showed normal voltage during SR. Of the 7 patients with moderate “scarring”, 2 patients showed normal voltage during SR, while in the remaining 5 “scarring” was only mild during SR. 3 patients showed extensive “scarring” during AF, which was only moderate during SR. During AF, areas of low voltage were more commonly observed in the PW (12/14) followed by the IW (6/14) and antero-septum (4/14); while in SR, in the antero-septum (4/8), PW (3/8) and IW (3/8). Interestingly, in all patients both the PW/IW and (less dramatically) the antero-septum showed more “scarring” during AF as compared to SR. Conclusion: Areas of low voltage are more severe and diffuse during AF when compared to SR. When areas of low voltage are detected during AF, they are more commonly seen in the PW, IW and antero-septal areas.

Catheter Ablation of Low-Voltage Areas for Persistent Atrial Fibrillation: Procedural Outcomes Using High-Density Voltage Mapping

2020 ◽  
Vol 36 (12) ◽  
pp. 1956-1964 ◽  
Author(s):  
Pablo B. Nery ◽  
Wael Alqarawi ◽  
Girish M. Nair ◽  
Mouhannad M. Sadek ◽  
Calum J. Redpath ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Low Voltage ◽  
Persistent Atrial Fibrillation ◽  
High Density ◽  
Voltage Mapping ◽  
Procedural Outcomes

Abstract 3068: Intra-left Ventricular Contractile Dyssynchrony As An Independent Determinant Of Left Atrial Remodeling In Patients With Atrial Fibrillation Managed by Catheter-based Circumferential Pulmonary Venous Isolation

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
FU-CHUN CHIU ◽  
Yi-Chih Wang ◽  
Chih-Chieh Yu ◽  
Ling-Ping Lai ◽  
Juey-Jen Hwang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Catheter Ablation ◽  
Sinus Rhythm ◽  
Left Atrial ◽  
Left Ventricular ◽  
Filling Pressure ◽  
Doppler Imaging ◽  
Atrial Remodeling ◽  
Independent Determinant

BACKGROUND. Enlarged left atrial volume (LAV), resulting from multifactorial pathogenesis, carries a poorer prognosis to patients with atrial fibrillation (AF) even under well rhythm control. We hypothesized that the preexistence of intra-left ventricular (LV) contractile dyssynchrony impaired diastolic filling, which contribute to atrial remodeling in AF patients. METHODS. We investigated 40 patients (34 men and 6 women, mean age 60 ± 10 years) with paroxysmal or persistent AF who were converted mainly by catheter ablation-based circumferential pulmonary venous isolation and then pharmacologically maintained in sinus rhythm. Exclusion criteria included significant (>moderate) valvular heart disease, LV ejection fraction <55 %, or ischemic heart disease confirmed by positive stress tests or coronary angiography. The LAV was measured by 2D echocardiography [π×D1×D2×D3/6 from parasternal long-axis view (D1) and apical four-chamber view (D2 & D3)]. The peak myocardial systolic velocity (S M ) and the time to peak S M (T S ) of the 6-basal and 6-mid LV segments were measured by tissue Doppler imaging (TDI). RESULTS. With similar AF duration before conversion, patients with LAV >40ml (n = 16) had similar baseline characteristics, cardiovascular medications, QRS width, and LV chamber sizes as those with LAV <40ml (n = 24). However, TDI showed the mean S M was borderline lower (6.3 ± 1.2 vs. 7.1 ± 1.2 cm/s, p < 0.05), and the maximal intersegmental difference in T S (77 ± 43 vs. 40 ± 22 ms, p < 0.003) was greater in patients with larger LAV. The intersegmental difference in T S correlated positively with LAV (r = 0.41, p < 0.009), and LV filling pressure estimated by early transmitral flow velocity/annular diastolic velocity was significantly higher (12.3 ± 7.8 vs. 8.7 ± 2.2, p < 0.045) in patients with intersegmental difference in T S >65 ms. After adjusting for age, gender, and the diastolic parameters, intersegmental difference in T S >65ms emerged as an independent determinant of larger LAV in multivariate logistic analysis (OR=17; 95% CI=2–166, p < 0.016). CONCLUSIONS. Intraventricular dyssynchrony, which accompanied with elevated LV filling pressure, contributed independently to LA remodeling in AF patients converted into sinus rhythm by catheter ablation.

scholarly journals Clinical Outcomes of low-voltage area-guided left atrial linear ablation for non-paroxysmal atrial fibrillation patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260834
Author(s):  
Hao-Tien Liu ◽  
Chia-Hung Yang ◽  
Hui-Ling Lee ◽  
Po-Cheng Chang ◽  
Hung-Ta Wo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Paroxysmal Atrial Fibrillation ◽  
Left Atrial ◽  
Low Voltage ◽  
Reverse Remodeling ◽  
Voltage Mapping ◽  
Linear Ablation

Background The therapeutic effect of low-voltage area (LVA)-guided left atrial (LA) linear ablation for non-paroxysmal atrial fibrillation (non-PAF) is uncertain. We aimed to investigate the efficacy of LA linear ablation based on the preexisting LVA and its effects on LA reverse remodeling in non-PAF patients. Methods We retrospectively evaluated 145 consecutive patients who underwent radiofrequency catheter ablation for drug-refractory non-PAF. CARTO-guided bipolar voltage mapping was performed in atrial fibrillation (AF). LVA was defined as sites with voltage ≤ 0.5 mV. If circumferential pulmonary vein isolation couldn’t convert AF into sinus rhythm, additional LA linear ablation was performed preferentially at sites within LVA. Results After a mean follow-up duration of 48 ± 33 months, 29 of 145 patients had drugs-refractory AF/LA tachycardia recurrence. Low LA emptying fraction, large LA size and high extent of LVA were associated with AF recurrence. There were 136 patients undergoing LA linear ablation. The rate of linear block at the mitral isthmus was significantly higher via LVA-guided than non-LVA-guided linear ablation. Patients undergoing LVA-guided linear ablation had larger LA size and higher extent of LVA, but the long-term AF/LA tachycardia-free survival rate was higher than the non-LVA-guided group. The LA reverse remodeling effects by resuming sinus rhythm were noted even in patients with a diseased left atrium undergoing extensive LA linear ablation. Conclusions LVA-guided linear ablation through targeting the arrhythmogenic LVA and reducing LA mass provides a better clinical outcome than non-LVA guided linear ablation, and outweighs the harmful effects of iatrogenic scaring in non-PAF patients.

scholarly journals Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation

2021 ◽  
Vol 129 (8) ◽  
pp. 804-820
Author(s):  
Stephan R. Künzel ◽  
Maximilian Hoffmann ◽  
Silvio Weber ◽  
Karolina Künzel ◽  
Susanne Kämmerer ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Knockout Mice ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
De Novo ◽  
Low Voltage ◽  
Human Fibroblasts ◽  
Right Atrial ◽  
Atrial Fibrosis

Rationale: Fibrosis promotes the maintenance of atrial fibrillation (AF), making it resistant to therapy. Improved understanding of the molecular mechanisms leading to atrial fibrosis will open new pathways toward effective antifibrotic therapies. Objective: This study aims to decipher the mechanistic interplay between PLK2 (polo-like kinase 2) and the profibrotic cytokine OPN (osteopontin) in the pathogenesis of atrial fibrosis and AF. Methods and Results: Atrial PLK2 mRNA expression was 10-fold higher in human fibroblasts than in cardiomyocytes. Compared with sinus rhythm, right atrial appendages and isolated right atrial fibroblasts from patients with AF showed downregulation of PLK2 mRNA and protein, along with increased PLK2 promotor methylation. Genetic deletion as well as pharmacological inhibition of PLK2 induced profibrotic phenotype conversion in cardiac fibroblasts and led to a striking de novo secretion of OPN. Accordingly, PLK2-deficient (PLK2 knockout) mice showed cardiac fibrosis and were prone to experimentally induced AF. In line with these findings, OPN plasma levels were significantly higher only in patients with AF with atrial low-voltage zones (surrogates of fibrosis) compared with sinus rhythm controls. Mechanistically, we identified ERK1/2 as the relevant downstream mediator of PLK2 leading to increased OPN expression. Finally, oral treatment with the clinically available drug mesalazine, known to inhibit ERK1/2, prevented cardiac OPN overexpression and reversed the pathological PLK2 knockout phenotype in PLK2 knockout mice. Conclusions: Abnormal PLK2/ERK1/2/OPN axis function critically contributes to AF-related atrial fibrosis, suggesting reinforcing PLK2 activity and/or OPN inhibition as innovative targets to prevent fibrosis progression in AF. Mesalazine derivatives may be used as lead compounds for the development of novel anti-AF agents targeting fibrosis.

Abstract 17261: Maintenance of Sinus Rhythm After His Bundle Pacing and AV Nodal Ablation in Patients With Recurrent Atrial Fibrillation After Catheter Ablation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Amrish Deshmukh ◽  
Puspha Khanal ◽  
Amlish Gondal ◽  
Mary Romanyshyn ◽  
Pramod Deshmukh
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Sinus Rhythm ◽  
Cardiac Resynchronization ◽  
Atrial Remodeling ◽  
Clinical Recurrence ◽  
His Bundle ◽  
His Bundle Pacing ◽  
Recurrent Atrial Fibrillation

Background: Catheter ablation (CA) is the most effective means of rhythm control for atrial fibrillation (AF) but is not curative. Irregular and rapid ventricular activation by AF begets AF. Cardiac resynchronization and atrioventricular nodal (AVN) ablation have been associated with favorable atrial remodeling and spontaneous reversion to sinus rhythm in patients with longstanding atrial fibrillation. Hypothesis: We hypothesized that in patients with longstanding persistent AF who had failed CA, AVN ablation and His bundle pacing (HBP) may improve maintenance of sinus rhythm. Methods and Results: A total of 13 patients (5 female, age 69±8.7 years, 8 with HFrEF, BMI 29 ±5 kg/m 2 ,LVEF 38±15%, NYHA 3±0.6) underwent simultaneous AVN ablation and HBP an average of 531 days (Range 1-2158 days) after CA for AF with recurrent AF. Prior to AVN ablation and HBP these patients had a median 9-year history of AF (IQR: 5-15 years) with a median of 2 prior cardioversions (IQR: 1-4) and 2 prior CA. All patients had failed at least 1 antiarrhythmic drug. In 3 patients HBP induced cardiac resynchronization of pre-existing bundle branch block and in 8 patients HBP was fused with ventricular pacing to optimize QRS duration. 12 of 13 patients had an atrial lead. All patients underwent cardioversion at the time of the procedure. In a median of follow up of 21 months (IQR:4-74 months), 7 of the 13 patients (54%) had no device detected or clinical recurrence of AF. In follow up LVEF increased to 46±12.7% and NYHA class to 2 ±0.2. Of patients with recurrence, 3 underwent CA and had no recurrence of AF in subsequent follow up. Conclusion: In patients with advanced longstanding persistent AF, a strategy of AVN ablation and HBP allowed for ventricular rate control with a narrow QRS. This approach resulted in a lower than expected rate of AF recurrence.

scholarly journals Atrial Myopathy Underlying Atrial Fibrillation

2020 ◽  
Vol 9 (2) ◽  
pp. 61-70
Author(s):  
Harold Rivner ◽  
Raul D Mitrani ◽  
Jeffrey J Goldberger ◽  
◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Cardiac Mri ◽  
Vicious Cycle ◽  
Atrial Fibrosis ◽  
Plasma Biomarkers ◽  
Voltage Mapping ◽  
Assessment And Treatment ◽  
Current Therapies ◽  
Current Assessment

While AF most often occurs in the setting of atrial disease, current assessment and treatment of patients with AF does not focus on the extent of the atrial myopathy that serves as the substrate for this arrhythmia. Atrial myopathy, in particular atrial fibrosis, may initiate a vicious cycle in which atrial myopathy leads to AF, which in turn leads to a worsening myopathy. Various techniques, including ECG, plasma biomarkers, electroanatomical voltage mapping, echocardiography, and cardiac MRI, can help to identify and quantify aspects of the atrial myopathy. Current therapies, such as catheter ablation, do not directly address the underlying atrial myopathy. There is emerging research showing that by targeting this myopathy we can help decrease the occurrence and burden of AF.

scholarly journals Low-Voltage Zones as the Atrial Fibrillation Substrates: Relationship With Initiation, Perpetuation, and Termination

2021 ◽  
Vol 8 ◽  
Author(s):  
Zheng Liu ◽  
Yu Xia ◽  
Changyan Guo ◽  
Xiaofeng Li ◽  
Pihua Fang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Distribution Pattern ◽  
Left Atrium ◽  
Surface Area ◽  
Low Voltage ◽  
Posterior Wall ◽  
Anterior Wall ◽  
Voltage Mapping ◽  
Significant Difference

Background: Low-voltage zones (LVZs) were usually targeted for ablation in atrial fibrillation (AF). However, its relationship with AF initiation, perpetuation, and termination remains to be studied. This study aimed to explore such relationships.Methods: A total of 126 consecutive AF patients were enrolled, including 71 patients for AF induction protocol and 55 patients for AF termination protocol. Inducible and sustainable AF were defined as induced AF lasting over 30 and 300 s, respectively. Terminable AF was defined as those that could be terminated into sinus rhythm within 1 h after ibutilide administration. Voltage mapping was performed in sinus rhythm for all patients. LVZ was quantified as the percentage of the LVZ area (LVZ%) to the left atrium surface area.Results: The rates of inducible, sustainable, and terminable AF were 29.6, 18.3, and 38.2%, respectively. Inducible AF patients had no significant difference in overall LVZ% compared with uninducible AF patients (10.2 ± 11.8 vs. 8.5 ± 12.6, p = 0.606), while sustainable and interminable AF patients had larger overall LVZ% than unsustainable (16.2 ± 11.5 vs. 0.5 ± 0.7, p &lt; 0.001) and terminable AF patients (44.6 ± 26.4 vs. 26.3 ± 22.3, p &lt; 0.05), respectively. The segmental LVZ distribution pattern was diverse in the different stages of AF. Segmental LVZ% difference was initially observed in the anterior wall for patients with inducible AF, and the septum was further affected in those with sustainable AF, and the roof, posterior wall, and floor were finally affected in those with interminable AF.Conclusions: The associations between LVZ with AF initiation, perpetuation, and termination were different depending on its size and distribution.

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