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Cardiovascular Research Jun 2021Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is... (Observational Study)
Observational Study
AIMS
Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is causally linked to AF pathogenesis in obesity remains elusive. We recently demonstrated that the constitutive activation of the 'NACHT, LRR, and PYD Domains-containing Protein 3' (NLRP3) inflammasome promotes AF susceptibility. In this study, we hypothesized that the NLRP3 inflammasome is a key driver of obesity-induced AF.
METHODS AND RESULTS
Western blotting was performed to determine the level of NLRP3 inflammasome activation in atrial tissues of obese patients, sheep, and diet-induced obese (DIO) mice. The increased body weight in patients, sheep, and mice was associated with enhanced NLRP3-inflammasome activation. To determine whether NLRP3 contributes to the obesity-induced atrial arrhythmogenesis, wild-type (WT) and NLRP3 homozygous knockout (NLRP3-/-) mice were subjected to high-fat-diet (HFD) or normal chow (NC) for 10 weeks. Relative to NC-fed WT mice, HFD-fed WT mice were more susceptible to pacing-induced AF with longer AF duration. In contrast, HFD-fed NLRP3-/- mice were resistant to pacing-induced AF. Optical mapping in DIO mice revealed an arrhythmogenic substrate characterized by abbreviated refractoriness and action potential duration (APD), two key determinants of reentry-promoting electrical remodeling. Upregulation of ultra-rapid delayed-rectifier K+-channel (Kv1.5) contributed to the shortening of atrial refractoriness. Increased profibrotic signaling and fibrosis along with abnormal Ca2+ release from sarcoplasmic reticulum (SR) accompanied atrial arrhythmogenesis in DIO mice. Conversely, genetic ablation of Nlrp3 (NLRP3-/-) in HFD-fed mice prevented the increases in Kv1.5 and the evolution of electrical remodeling, the upregulation of profibrotic genes, and abnormal SR Ca2+ release in DIO mice.
CONCLUSION
These results demonstrate that the atrial NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmogenesis and establishes a mechanistic link between obesity-induced AF and NLRP3-inflammasome activation.
Topics: Action Potentials; Aged; Animals; Atrial Fibrillation; Calcium Signaling; Case-Control Studies; Disease Models, Animal; Female; Heart Atria; Heart Rate; Humans; Inflammasomes; Inflammation; Kv1.5 Potassium Channel; Male; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Obesity; Sheep, Domestic; Mice
PubMed: 33523143
DOI: 10.1093/cvr/cvab024 -
Europace : European Pacing,... Feb 2023The long-term success rate of ablation therapy is still sub-optimal in patients with persistent atrial fibrillation (AF), mostly due to arrhythmia recurrence originating...
AIMS
The long-term success rate of ablation therapy is still sub-optimal in patients with persistent atrial fibrillation (AF), mostly due to arrhythmia recurrence originating from arrhythmogenic sites outside the pulmonary veins. Computational modelling provides a framework to integrate and augment clinical data, potentially enabling the patient-specific identification of AF mechanisms and of the optimal ablation sites. We developed a technology to tailor ablations in anatomical and functional digital atrial twins of patients with persistent AF aiming to identify the most successful ablation strategy.
METHODS AND RESULTS
Twenty-nine patient-specific computational models integrating clinical information from tomographic imaging and electro-anatomical activation time and voltage maps were generated. Areas sustaining AF were identified by a personalized induction protocol at multiple locations. State-of-the-art anatomical and substrate ablation strategies were compared with our proposed Personalized Ablation Lines (PersonAL) plan, which consists of iteratively targeting emergent high dominant frequency (HDF) regions, to identify the optimal ablation strategy. Localized ablations were connected to the closest non-conductive barrier to prevent recurrence of AF or atrial tachycardia. The first application of the HDF strategy had a success of >98% and isolated only 5-6% of the left atrial myocardium. In contrast, conventional ablation strategies targeting anatomical or structural substrate resulted in isolation of up to 20% of left atrial myocardium. After a second iteration of the HDF strategy, no further arrhythmia episode could be induced in any of the patient-specific models.
CONCLUSION
The novel PersonAL in silico technology allows to unveil all AF-perpetuating areas and personalize ablation by leveraging atrial digital twins.
Topics: Humans; Atrial Fibrillation; Treatment Outcome; Tachycardia, Supraventricular; Heart Atria; Computer Simulation; Pulmonary Veins; Catheter Ablation; Recurrence
PubMed: 35943361
DOI: 10.1093/europace/euac116 -
Methodist DeBakey Cardiovascular Journal Apr 2021Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of all-cause mortality and complications. The autonomic nervous... (Review)
Review
Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of all-cause mortality and complications. The autonomic nervous system (ANS) plays a central role in AF, with the heart regulated by both extrinsic and intrinsic properties. In the extrinsic ANS, the sympathetic fibers are derived from the major paravertebral ganglia, especially the stellate ganglion (SG), which is a source of cardiac sympathetic innervation since it connects with multiple intrathoracic nerves and structures. The major intrinsic ANS is a network of axons and ganglionated plexi that contains a variety of sympathetic and parasympathetic neurons, which communicate with the extrinsic ANS. Simultaneous sympathovagal activation contributes to the development of AF because it increases calcium entry and shortens the atrial action potential duration. In animal and human studies, neuromodulation methods such as electrical stimulation and renal denervation have indicated potential benefits in controlling AF in patients as they cause SG remodeling and reduce sympathetic outflow. This review focuses on the neural mechanisms relevant to AF and the recent developments of neuromodulation methods for AF control.
Topics: Ablation Techniques; Action Potentials; Animals; Atrial Fibrillation; Autonomic Nervous System; Calcium Signaling; Electric Stimulation Therapy; Heart Atria; Heart Rate; Humans; Sympathectomy; Treatment Outcome
PubMed: 34104319
DOI: 10.14797/FVDN2224 -
Europace : European Pacing,... Aug 2023The amount of fibrosis in the left atrium (LA) predicts atrial fibrillation (AF) recurrence after catheter ablation (CA). We aim to identify whether regional variations... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
The amount of fibrosis in the left atrium (LA) predicts atrial fibrillation (AF) recurrence after catheter ablation (CA). We aim to identify whether regional variations in LA fibrosis affect AF recurrence.
METHODS AND RESULTS
This post hoc analysis of the DECAAF II trial includes 734 patients with persistent AF undergoing first-time CA who underwent late gadolinium enhancement magnetic resonance imaging (LGE-MRI) within 1 month prior to ablation and were randomized to MRI-guided fibrosis ablation in addition to standard pulmonary vein isolation (PVI) or standard PVI only. The LA wall was divided into seven regions: anterior, posterior, septal, lateral, right pulmonary vein (PV) antrum, left PV antrum, and left atrial appendage (LAA) ostium. Regional fibrosis percentage was defined as a region's fibrosis prior to ablation divided by total LA fibrosis. Regional surface area percentage was defined as an area's surface area divided by the total LA wall surface area before ablation. Patients were followed up for a year with single-lead electrocardiogram (ECG) devices. The left PV had the highest regional fibrosis percentage (29.30 ± 14.04%), followed by the lateral wall (23.23 ± 13.56%), and the posterior wall (19.80 ± 10.85%). The regional fibrosis percentage of the LAA was a significant predictor of AF recurrence post-ablation (odds ratio = 1.017, P = 0.021), and this finding was only preserved in patients receiving MRI-guided fibrosis ablation. Regional surface area percentages did not significantly affect the primary outcome.
CONCLUSION
We have confirmed that atrial cardiomyopathy and remodelling are not a homogenous process, with variations in different regions of the LA. Atrial fibrosis does not uniformly affect the LA, and the left PV antral region has more fibrosis than the rest of the wall. Furthermore, we identified regional fibrosis of the LAA as a significant predictor of AF recurrence post-ablation in patients receiving MRI-guided fibrosis ablation in addition to standard PVI.
Topics: Humans; Atrial Fibrillation; Contrast Media; Gadolinium; Heart Atria; Fibrosis; Catheter Ablation; Recurrence; Pulmonary Veins; Treatment Outcome
PubMed: 37428891
DOI: 10.1093/europace/euad199 -
Europace : European Pacing,... Nov 2023Areas of conduction inhomogeneity (CI) during sinus rhythm may facilitate the initiation and perpetuation of atrial fibrillation (AF). Currently, no tool is available to...
AIMS
Areas of conduction inhomogeneity (CI) during sinus rhythm may facilitate the initiation and perpetuation of atrial fibrillation (AF). Currently, no tool is available to quantify the severity of CI. Our aim is to develop and validate a novel tool using unipolar electrograms (EGMs) only to quantify the severity of CI in the atria.
METHODS AND RESULTS
Epicardial mapping of the right atrium (RA) and left atrium, including Bachmann's bundle, was performed in 235 patients undergoing coronary artery bypass grafting surgery. Conduction inhomogeneity was defined as the amount of conduction block. Electrograms were classified as single, short, long double (LDP), and fractionated potentials (FPs), and the fractionation duration of non-single potentials was measured. The proportion of low-voltage areas (LVAs, <1 mV) was calculated. Increased CI was associated with decreased potential voltages and increased LVAs, LDPs, and FPs. The Electrical Fingerprint Score consisting of RA EGM features, including LVAs and LDPs, was most accurate in predicting CI severity. The RA Electrical Fingerprint Score demonstrated the highest correlation with the amount of CI in both atria (r = 0.70, P < 0.001).
CONCLUSION
The Electrical Fingerprint Score is a novel tool to quantify the severity of CI using only unipolar EGM characteristics recorded. This tool can be used to stage the degree of conduction abnormalities without constructing spatial activation patterns, potentially enabling early identification of patients at high risk of post-operative AF or selection of the appropriate ablation approach in addition to pulmonary vein isolation at the electrophysiology laboratory.
Topics: Humans; Atrial Fibrillation; Heart Rate; Heart Atria; Epicardial Mapping; Atrioventricular Node
PubMed: 37931071
DOI: 10.1093/europace/euad324 -
Journal of the American Heart... Sep 2023Background Elevated left atrial (LA) pressure predisposes individuals to the initiation and persistence of atrial fibrillation (AF), and LA hypertension is associated...
Background Elevated left atrial (LA) pressure predisposes individuals to the initiation and persistence of atrial fibrillation (AF), and LA hypertension is associated with AF recurrence after catheter ablation (CA). However, the exact frequency and factors associated with LA hypertension are unknown, and its noninvasive estimation is challenging. This study aimed to investigate the prevalence and determinants of LA hypertension in patients with AF who underwent first CA. Methods and Results We examined 183 patients with AF who underwent conventional and speckle-tracking echocardiography before CA to assess LA size, reservoir strain, and stiffness. Direct LA pressure was measured at the time of CA, and LA hypertension was defined as mean LA pressure >15 mm Hg. Thirty-three (18.0%) patients exhibited LA hypertension. Patients with LA hypertension had a significantly larger LA volume index (40.2 [28.4-52.1] versus 34.1 [26.9-42.4] mL/m, =0.025), reduced LA reservoir strain (15.1 [10.4-21.7] versus 22.7 [14.4-32.3] %, =0.002) and increased LA stiffness (0.69 [0.34-0.99] versus 0.36 [0.24-0.54], <0.001). Multivariable analyses showed that waist circumference, C-reactive protein level, LA reservoir strain, and LA stiffness were independently associated with LA hypertension (all <0.05), while LA volume and E/e' ratio were not. Among echocardiographic parameters, receiver operating characteristic curve analysis identified LA stiffness as the best predictor of LA hypertension. Conclusions Approximately 20% of patients with AF who underwent CA had LA hypertension. Central obesity and inflammation might be involved in the pathophysiological mechanisms of LA hypertension, and echocardiography-derived LA stiffness may have clinical utility for the detection of LA hypertension before CA.
Topics: Humans; Atrial Fibrillation; Prevalence; Heart Atria; Echocardiography; Hypertension
PubMed: 37702280
DOI: 10.1161/JAHA.123.030325 -
International Journal of Cardiology Jul 2022Despite improvement in treatment strategies of atrial fibrillation (AF), a considerable number of patients still experience recurrence of atrial tachyarrhythmia (ATA)...
BACKGROUND
Despite improvement in treatment strategies of atrial fibrillation (AF), a considerable number of patients still experience recurrence of atrial tachyarrhythmia (ATA) following catheter ablation (CA). This study aimed to investigate the prognostic value of left atrial (LA) deformation analysis in a large group of patients undergoing CA for AF.
METHODS
This study included 678 patients with AF. Echocardiography including two-dimensional speckle tracking echocardiography (2DSTE) was performed in all patients prior to CA. Logistic regression analysis was used to assess the association between ATA recurrence and LA strain during reservoir phase (LASr), LA strain during contraction phase (LASct), and LA strain during conduit phase (LAScd).
RESULTS
During one-year follow-up, 274 (40%) experienced ATA recurrence. Median age of the included study population was 63.2 years (IQR: 55.5, 69.5) and 485 (72%) were male. Patients with recurrence had lower LASr (22.6% vs. 25.1%, p = 0.001) and LASct (10.7% vs. 12.4%, p < 0.001). No difference in LAScd was observed. After adjusting for potential clinical and echocardiographic confounders LASr (OR = 1.04, CI95% [1.01; 1.07], p = 0.015, per 1% decrease) and LASct (OR = 1.06, CI95% [1.02; 1.11], p = 0.007, per 1% decrease) remained independent predictors of recurrence. However, in patients with a normal-sized LA (LA volume index<34 mL/m), only LASct remained an independent predictor of recurrence (OR = 1.07, CI95% [1.01; 1.12], p = 0.012, per 1% decrease).
CONCLUSION
In patients undergoing CA for AF, LA deformation analysis by 2DSTE could be of use in risk stratification in clinical practice regarding ATA recurrence, even in patients with a normal-sized LA.
Topics: Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Female; Heart Atria; Humans; Male; Recurrence; Tachycardia; Treatment Outcome
PubMed: 35469934
DOI: 10.1016/j.ijcard.2022.04.056 -
JACC. Clinical Electrophysiology Mar 2021
Topics: Atrial Fibrillation; Catheter Ablation; Cicatrix; Embolic Stroke; Heart Atria; Humans
PubMed: 33736752
DOI: 10.1016/j.jacep.2020.12.002 -
BMC Cardiovascular Disorders Feb 2022Left atrial roof-dependent tachycardias (LARTs) are common macroreentrant atrial tachycardias (ATs). We sought to characterize clinical LARTs using an ultra-high...
BACKGROUND
Left atrial roof-dependent tachycardias (LARTs) are common macroreentrant atrial tachycardias (ATs). We sought to characterize clinical LARTs using an ultra-high resolution mapping system.
METHODS
This study included 22 consecutive LARTs in 21 patients who underwent AT mapping/ablation using Rhythmia systems.
RESULTS
Three, 13, 4, and 2 LART patients were cardiac intervention naïve (Group-A), post-roof line ablation (Group-B), post-atrial fibrillation ablation without linear ablation (Group-C), and post-cardiac surgery (Group-D), respectively. The mean AT cycle length was 244 ± 43 ms. Coronary sinus activation was proximal-to-distal or distal-to-proximal in 16 (72.7%) ATs. The activation map revealed 13 (59.1%) clockwise and 9 (40.9%) counter-clockwise LARTs. A 12-lead synchronous isoelectric interval was observed in 10/19 (52.6%) LARTs. The slow conduction area was identified on the LA roof, anterior/septal wall, and posterior wall in 18, 6, and 2 ATs, respectively. Twenty concomitant ATs among 13 procedures were also eliminated, and peri-mitral AT coexisted in 7 of 9 non-group-B patients. In group-B, the conduction gap was predominantly located on the mid-roof. Sustained LARTs were terminated by a single application and linear ablation in 6 (27.3%) and 9 (40.9%), while converting to other ATs in 7 (31.8%) LARTs. Complete linear block was created without any complications in all, however, ablation at the mid-posterior wall was required to achieve block in 4 (18.2%) procedures. During 14.0 (6.5-28.5) months of follow-up, 17 (81.0%) and 19 (90.5%) patients were free from any atrial tachyarrhythmias after single and last procedures.
CONCLUSIONS
The LART mechanisms were distinct in individual patients, and elimination of all concomitant ATs was required for the management.
Topics: Action Potentials; Aged; Aged, 80 and over; Catheter Ablation; Electrophysiologic Techniques, Cardiac; Female; Heart Atria; Heart Rate; Humans; Male; Middle Aged; Predictive Value of Tests; Recurrence; Tachycardia, Supraventricular; Time Factors; Treatment Outcome
PubMed: 35172730
DOI: 10.1186/s12872-022-02505-z -
International Journal of Molecular... Mar 2023ANP is mainly synthesized by the atria, and upon excretion, it serves two primary purposes: vasodilation and increasing the renal excretion of sodium and water. The... (Review)
Review
ANP is mainly synthesized by the atria, and upon excretion, it serves two primary purposes: vasodilation and increasing the renal excretion of sodium and water. The understanding of ANP's role in cardiac systems has improved considerably in recent decades. This review focuses on several studies demonstrating the importance of analyzing the regulations between the endocrine and mechanical function of the heart and emphasizes the effect of ANP, as the primary hormone of the atria, on atrial fibrillation (AF) and related diseases. The review first discusses the available data on the diagnostic and therapeutic applications of ANP and then explains effect of ANP on heart failure (HF) and atrial fibrillation (AF) and vice versa, where tracking ANP levels could lead to understanding the pathophysiological mechanisms operating in these diseases. Second, it focuses on conventional treatments for AF, such as cardioversion and catheter ablation, and their effects on cardiac endocrine and mechanical function. Finally, it provides a point of view about the delayed recovery of cardiac mechanical and endocrine function after cardioversion, which can contribute to the occurrence of acute heart failure, and the potential impact of restoration of the sinus rhythm by extensive ablation or surgery in losing ANP-producing sites. Overall, ANP plays a key role in heart failure through its effects on vasodilation and natriuresis, leading to a decrease in the activity of the renin-angiotensin-aldosterone system, but it is crucial to understand the intimate role of ANP in HF and AF to improve their diagnosis and personalizing the patients' treatment.
Topics: Humans; Atrial Fibrillation; Atrial Natriuretic Factor; Heart Atria; Heart Failure; Amyloidosis
PubMed: 37047444
DOI: 10.3390/ijms24076470