Sinus Rhythm Research Articles

Right atrial strain: the hidden proof of bi-atrial cardiomyopathy in AF patients?

Abstract Background Although assessment of left atrium (LA) abnormalities has been extensively studied in atrial fibrillation (AF), structural and functional changes in the right atrium (RA) have remained almost unexplored in this context. Purpose We investigated the role of bi-atrial strain in patients with AF undergoing catheter ablation (CA). Methods Fifty-six consecutive patients undergoing catheter ablation of AF were prospectively studied with speckle-tracking echocardiography and electrophysiological study, before and after CA (median follow-up: 7±3 months). A group of 32 subjects undergoing CA of paroxysmal atrioventricular node-reentrant tachycardia, without structural heart disease, served as control group. Results Patients with AF had worse LA, but also RA strain indexes compared to controls [RA strain parameters: peak RAS reservoir (pRASr): 22.1±12.6 vs 29.8±12.7%, p=0.009; RA dispersion: SD-regional-RA-time-to-peak (SD-regional-RA-TTP): 0.048±0.015 vs 0.038±0.009, p=0.020)]. Patients with persistent AF showed similar LA strain values, but worse RA strain indexes, compared to patients with paroxysmal AF (pRASr: 24.8±12.1 vs 15.9±11.7%,p=0.017; SD-regional-RA-TTP:0.043±0.023 vs 0.062±0.030, p=0.016). RA function showed a significant relation with both LA strain and volume indexes and with abnormal LA electroanatomical substrate (pRASr and pLASr, Pearson correlation: r 0.594, p< 0.001; pRASr and low-voltage LA area: -0.316, p=0.018). RA, but not LA, parameters were found significantly reduced in patients with AF recurrence post-CA compared to those who maintain sinus rhythm (pRASr: 14.1±11.7 vs 24.6±13.5, p=0.039; SD-regional-RA-TTP: 0.054±0.031 vs 0.032±0.010, p=0.002), while the only independent clinical predictor of AF recurrence remained cardiovascular risk profile (CHA2DS2 VASc Score: HR 1.47,CI 1.003-2.158, p= 0.048). Conclusion RA function, as assessed by strain imaging, resulted progressively impaired in worse subtypes of AF, showing a strong correlation with bi-atrial mechanical and electroanatomical parameters, and associated with AF recurrences post-ablation.Graphical Abstract

Efficacy and safety of ultrasound guided stellate ganglion block: developing new clinical indications beyond electrical storm

Abstract Background Percutaneous stellate ganglion block (PSGB) is recommended by the latest European guidelines for patients with drug and ventricular tachycardia (VT) ablation refractory electrical storm (ES). Yet, due to the strong antiarrhythmic potential, combined with the good safety profile, we’ve recently used it for to the prophylaxis of ventricular arrhythmias (VAs) in high-risk patients and the prophylaxis/treatment of atrial arrhythmias in patients with acute heart failure (HF). Purpose To describe our single-center experience with PSGB usage outside the conventional indication of ES. Methods We hereby describe our single center experience with PSGB from 2/2021 to 2/2024. Results 56 patients (87% male, mean age 64 ± 12 years) received a total of 91 PSGB performed with the lateral, ultrasound (US) guided technique. Most of the procedures consisted of a single bolus anesthetic injection of lidocaine plus ropivacaine, 27% in an additional continuous infusion, mainly with ropivacaine. All procedures except for 3 in a single patient who had previously received left cardiac sympathetic denervation, were performed on the left side. Most of the patients (61%) suffered ischemic cardiomyopathy (CMP), including 11 with an acute coronary syndrome; the rest had non-ischemic CMP. 63 PSGB (69%) were performed in patients with impending or manifested cardiogenic shock (SCAI classification B or more). Mean LVEF was 24 ± 12%. Most of the procedures (n=80, 88%) were performed due to ongoing refractory VAs, yet 6 (6%) aimed to prevent major VAs in high-risk patients, mostly in the setting of recent ES (within 1 month) and need for Levosimendan to support cardiac output, in one case due to recent stereotactic VT ablation, to prevent early VAs in the phase of acute radiation induced microvascular damage. All 6 were effective in preventing clinically significant VAs. Additionally, 5 single bolus PSGBs (5%) were performed due to atrial arrhythmias with high ventricular rate despite intravenous drugs in the setting of acute HF. Specifically, 3 patients had atrial fibrillation (AF), 1 patient runs of ectopic atrial tachycardia (AT) and 1 patient 2:1 atrial flutter. Left-sided PSGB significantly reduced (≥25% reduction) ventricular rate during AF and AT but not during the single case of 2:1 atrial flutter, in 2/3 AF cases a cardioversion into sinus rhythm occurred within 40 minutes from PSGB. Only 1 (1%) major complication occurred (respiratory arrest), that was quickly and effectively treated with lipid emulsion, while minor complications were observed in 11% of PSGBs (mostly transient left arm weakness). Conclusions Our data suggest that US-guided PSGB usage, thanks to its feasibility at bed-side and good safety profile, may expand, beyond ES, to not only VAs prevention in high-risk settings, but also to prophylaxis/treatment of atrial arrhythmias in critically ill patients with acute heart failure requiring concomitant inotropic support.

Clinical findings from a large endo-epicardial atrial arrhythmia ablation registry

Abstract Background Despite advances, catheter ablation success rates for persistent AF remain at 50-60%. The approach for recurrent persistent AF, beyond pulmonary vein isolation, remains contentious. Surgical maze procedures have demonstrated superior outcomes compared to catheter ablation. Catheter-based linear lesions sets have failed to demonstrate efficacy, perhaps due to a lack of consistent transmurality with endocardial radiofrequency. Objective We report our safety and clinical data of an endo-epicardial approach using high-power radiofrequency ablation for atrial arrhythmias. Methods 126 patients (80% male; mean age 65 years [43-81]) underwent redo ablation, between August 2020 and February 2024, for recurrent symptomatic atrial arrhythmias using an endo-epicardial approach. We used a standardised linear lesion set (posterior wall isolation and anterior mitral line) for recurrent persistent AF. Results Utilising an intentional coronary sinus exit and C02 insufflation technique, we achieved epicardial access in 121 anti-coagulated patients. 5 patients were found to have pericardial adhesions, prohibiting access. There were 2 LIMA punctures which were coiled, 2 cases of excess pericardial bleeding (not access related), that settled conservatively, and no surgery or death. 92% of patients received epicardial ablation. 86 anterior mitral lines (95% acute block, 79% with epi ablation), 88 roof lines (92% blocked, 50% with epi ablation) and 81 floor lines (98% blocked, 36% with epi ablation) were undertaken. 106 posterior wall isolations were performed (94% isolated, 51% epi ablation). 75 patients had a standardised lesion set and were included for recurrence analysis. 49 had persistent AF (71% male, mean age 65 years, mean LAVI 38 ml/m2, 26 PVI at baseline and 23 PV reconnections) and 26 longstanding persistent AF (92% male, median age 64 years, mean LAVI 37.1 mls/m2, 16 PVI at baseline and 10 PV reconnections). 82% with persistent AF (median follow up time 11 months) and 38% with longstanding persistent AF (median follow up time 10.1 months) maintained sinus rhythm. The submitted image demonstrates the freedom from persistent AF, for the cohort who are beyond the 3-month blanking period, as per classification of atrial arrhythmia. Conclusion In one the largest cohorts to date, we have shown that endo-epicardial atrial ablation is feasible and safe with epicardial ablation allowing improved transmurality and thus acute linear block. Clinical outcomes, using a posterior wall isolation and anterior mitral line, were favourable for persistent but not longstanding persistent AF.

Could piano music therapy alleviate high sinus rhythm in subjects with controlled hypertension?

Abstract Background/Introduction With a millenary tradition, music is rediscovered nowadays, as adjuvant therapy. The number of beats per minute (bpm) is the common factor of cardiology – representing heart rate (HR), and music – reprezentative for tempo. Purpose Our goal was the HR modulation in patients (pts) with moderate tachycardia using three piano kits: K1 – Adagio by Albinoni, K2 – Piano Concerto nr. 21 by Mozart, second part; and K3 – Liebestraum by Liszt. Methods During 1st January – 31st December 2023, we identified by ambulatory screening 288 pts adequate for our goal. As exclusion criterion, we considered any type of rhythm or conduction dysturbances. All selected pts were controlled with antihypertensive agents not altering HR, usually thiazide/thiazide-like diuretics and/or ACEis/ARBs. The study group consisted in 144 hypertensive pts controlled at least six months, without any other cardiac diseases. The control group consisted in 144 pts with normal cardiologic examination. Both groups were demographically balanced. The HR at admission was between 84 and 120 bpm, the pts being stratified in three bpm subcategories. All pts have done three visits consisting in: physical examination, ECG, lab markers, TTE for V1 at initiation and EoS at six months, and respectively, physical exam and ECG for V2 at 3 months. Results (in bpm): Inside the group with HR 84-96 treated with K1, the Controlled HTN group (CHG) and the Normal Cardiac group (NCG) alleviated HR from 85,8 +/- 12,6 to 82,6 +/- 12,2; and from 85,7 +/- 12,6 to 80,8 +/- 11,9, respectively. For pts inside the interval 97-108 treated with K1, the CHG group and the NCG alleviated HR from 94,3 +/- 14,1 to 90,9 +/- 13,7 and, respectively, from 94,4 +/- 14,1 to 89,7 +/- 13,6. In pts from HR spectrum 97-108 treated with K2, the CHG and the NCG alleviated HR from 98,4 +/- 14,6 to 95,7 +/- 14,1; and from 98,5 +/- 14,6 to 94,1 +/- 13,8; respectively. Inside the group with HR spectrum 109-120 treated with K1, the CHG and the NCG alleviated HR from 97,1 +/- 14,3 to 94,8 +/- 13,9; and, respectively, from 97,0 +/- 14,3 to 93,9 +/- 13,7. For pts inside the interval 109-120 treated with K2, the CHG and the NCG alleviated HR from 101,7 +/- 14,6 to 99,3 +/- 14,2; and from 101,8 +/- 14,6 to 97,3 +/- 14,1; respectively. In pts from HR spectrum 109-120 treated with K3, the CHG and the NCG alleviated HR from 106,1 +/- 14,7 to 103,8 +/- 14,6; and from 106,5 +/- 14,4 to 103,6 +/- 14,4; respectively. Conclusions The effect of piano music on HR seems favorable in controlled hypertensive pts without major comorbidities, probably by interfering the sympathetic vegetative nervous system. In this regard, it could be used as adjuvant in optimizing this cardiac parameter. However, a multicentered randomized clinical study will be needed.

Procedural outcomes of fluoroscopy-less catheter ablation for atrial fibrillation

Abstract Background Radiofrequency catheter ablation is superior therapy to antiarrhythmic drugs for maintaining sinus rhythm in atrial fibrillation (AF) patients. Traditional fluoroscopy-guided AF ablation poses risks of prolonged radiation exposure for both patients and medical staff. Recent advancements in fluoroscopy-less catheter ablation techniques offer potential solutions, but comprehensive data on their effectiveness and safety are lacking. Purpose To evaluate the procedural outcomes and safety of fluoroscopy-less catheter ablation for AF compared to fluoroscopy-guided ablation. Methods Retrospective observational study of consecutive AF ablations (N=881) conducted at a university teaching hospital (Hamilton Health Sciences, Hamilton, Ontario) from November 2017 to September 2022. An electro-anatomical mapping system and ICE was used in all cases. Baseline characteristics and procedural outcomes between the fluoroscopy-less and fluoroscopy-guided groups were compared. Cases that used <60 seconds of fluoroscopy (occasionally used by operators during the placement of an esophageal probe) were included in the fluoroscopy-less group (N= 68). Results Mean age of individuals was 60.6 ± 11 years, 71.7% were male, 72.6% had paroxysmal AF, mean CHA2DS2-VASc score was 1.6 ± 1.4, 11.1% had prior heart failure, and mean left ventricular ejection fraction was 57.5 ± 15%. There were no significant differences in patient baseline characteristics between the fluoroscopy-less and fluoroscopy groups. Total procedure and fluoroscopy times were lower in the fluoroscopy-less group compared to the fluoroscopy-guided group (169.3 ±42 minutes vs. 192.1 ±54 minutes, p<0.0001 and 0.024 ±0.10 vs. 10.0 ±7.4 minutes , p<0.0001). Fluoroscopy-less AF ablation remained an independent predictor of lower procedure times following adjusting for the use of general anesthesia, high-power short-duration, presence of trainees, AF pattern, redo cases, and type of mapping system. Complication rates were similar between fluoroscopy-less and fluoroscopy-guided ablation (1.9% vs. 3.8%, p=0.11). Conclusion Fluoroscopy-less catheter ablation for AF appears to have similar procedural outcomes and safety than fluoroscopy-guided AF ablation.

Long-term follow-up after catheter ablation of atrial fibrillation and atrial tachycardia in patients with pulmonary hypertension

Abstract Introduction Catheter ablation of atrial fibrillation and atrial tachycardia (AF / AT) is established treatment in selected population. Only limited data, including long-term results, exist in patients with pulmonary hypertension (PH). Recently published prospective multicentric trial showed that more extensive radiofrequency catheter ablation of the bi-atrial arrhythmogenic substrate instead of clinical arrhythmia ablation alone is not beneficial in terms of arrhythmia recurrence in patients with AF / AT and PH. Now, we present the results of an extended, long-term follow-up from one of the study centres. Methods Patients with combined post- and pre-capillary or isolated pre-capillary PH and AF / AT indicated to catheter ablation were enrolled and randomised 1:1 into two parallel treatment arms. Patients underwent either clinical arrhythmia ablation only (Limited ablation group) or clinical arrhythmia plus substrate-based ablation (Extended ablation group). The primary endpoint was arrhythmia recurrence >30 s without antiarrhythmic drugs after the 3-month blanking period. Results A total of 52 patients (median age 71 years (IQR 62-75); 27 males) were enrolled. The presumable clinical arrhythmia was AF in 20 and AT in 32 patients, including typical AFL in 22 patients. Limited and extended ablation group included 28 and 24 patients, respectively. During the extended follow-up period of median 31 (IQR: 18; 46) months, the primary endpoint occurred in 17 patients (71 %) vs. 13 patients (46 %) in the Extended vs. Limited ablation group (p = 0.096). In parallel, overall mortality was comparable between groups (9 [38 %] vs. 11 [39 %]). Only 2 patients had recurrence of AFL during the extended follow-up. However, new different arrhythmia was documented in another 7 patients after the AFL ablation. Conclusion In PH patients, recurrence of AF / AT after a catheter ablation is frequent and the recurrence rate increases with the duration of follow-up. Ablation strategy seems to have no impact on arrhythmia free survival. Patients with typical atrial flutter have significantly higher chance to maintain sinus rhythm after a catheter ablation compared to AF or other AT.

Comparison of characteristics and acute ablation outcome of atrial fibrillation drivers detected using octaray vs. pentaray catheter

Abstract Background Atrial fibrillation (AF) driver ablation is proposed as treatment strategy beyond pulmonary vein (PV) isolation in persistent AF patients. The CARTOFINDER mapping system (Biosense Webster Inc.) can depict two types of activation patterns, focal and rotational activation, using unipolar potentials during AF. Recently, an 8-spline 48-electrodes mapping catheter (OctaRay) was developed. Purpose To evaluate the characteristics of AF drivers detected by CARTOFINDER using the OctaRay catheter and the acute termination compared to previous mapping catheter (PentaRay). Methods This is a multicenter prospective observational study from 6 hospitals where 47 persistent AF patients underwent initial catheter ablation from April to December 2023. We assessed the frequency and distribution of AF drivers in both atrium identified by CARTOFINDER using the OctaRay catheter before procedure. After PV isolation, additional ablation was performed on high-repetitive activations (focal activation>22 repetitions, rotational activation>17 repetitions) and the rate of acute AF termination was evaluated. Acute AF termination was defined as transition to sinus rhythm or atrial tachycardia (AT). The results were compared to 29 patients in whom the PentaRay catheter was used from September 2022 to March 2023. Results The mean age of OctaRay group was 72.0±8.6 years. The median AF duration was 0.7 years, and the prevalence of long-standing AF was 26%. All clinical characteristics was not significantly different between OctaRay and PentaRay group. Focal activation was more frequently identified in OctaRay group than in PentaRay group (94.1points/patient vs. 36.3points/patient, P<0.01), especially in anterior (P<0.01) and posterior (P<0.01) of right atrium (RA), posterior (P<0.01), roof (P<0.01) and lateral (P<0.01) of left atrium (LA), and PV antrum (P<0.01), respectively. Rotational activation was also more frequently identified in OctaRay group (54.7points/patient vs. 2.6points/patient, P<0.01), especially in anterior (P=0.02) and posterior (P=0.03) of RA, and anterior of LA (P=0.02), respectively. Furthermore, high-repetitive focal activation was more frequently identified in OctaRay group than in PentaRay group (P<0.01). On the other hand, the frequency of high-repetitive rotational activation was not significantly different between the two groups (P=0.63) (Figure A). In OctaRay group, high-repetitive focal activation was frequent in anterior of RA (72.3%) and LA appendage (48.9%) (Figure B), and had significantly shorter AF cycle length compared to the entire atrium (156ms vs. 162ms, P<0.01). Ablation for high-repetitive activations after PV isolation resulted in 12.8% acute AF termination in OctaRay group, significantly higher than in PentaRay group (vs. 0%, P=0.04). Conclusion The OctaRay catheter have the potential to detect more frequent and accurate AF drivers than the PentaRay catheter, leading to the improvement of acute AF termination.

Integrating single-cell sequencing and genetic lineage tracing reveals endothelial plasticity during atrial remodeling

Abstract Background Atrial fibrillation (AF), as the most burdensome cardiac arrhythmia, could lead to the significant mortality and morbidity. Atrial fibrosis is a well-recognized pathophysiological factor of the development and progression of AF, which also hampers its treatment. However, the underlying mechanisms of this intricate process remain largely unknown. Purpose This study sought to reveal the cellular composition of AF substrate and investigate the vital contributors to atrial structural remodeling. Methods Left atrial appendages from three patients with AF undergoing surgical ablation and three individuals with sinus rhythm undergoing heart transplantation were subjected to 10X single-cell RNA sequencing (scRNA-seq). Another five public scRNA-seq or snRNA-seq datasets of potentially remodeled right or left appendages were retrieved across three publications. The vital contributors of atrial structural remodeling and their characteristics were identified by intercellular communication analysis and trajectory inference. Transverse aortic constriction (TAC) was used to induce atrial remodeling in Cdh5-CreERT2;RFP mice, followed by scRNA-seq of endothelial cells (ECs). Human primary atrial ECs and fibroblasts were isolated for cell-cell interaction experiments. ECs-specific mouse models of Transforming growth factor beta 1 (TGFB1) (knockout and overexpression) were generated. Electrophysiological and histology analyses were performed to determine the consequences of ECs-derived TGFB1 gain and loss of function in the atrium. Results The comprehensive analysis of different scRNA-seq datasets revealed that ECs played an important regulatory role in the homeostasis of atrial substrate and displayed remarkable mesenchymal activation during atrial remodeling, which was further confirmed by TAC mice. Immunofluorescence staining and high-content screening suggested that the complete transition from ECs to mesenchymal cells slightly contributed to atrial remodeling. However, TGFB1 secreted from mesenchymal activated ECs significantly promoted activation, proliferation, and collagen secretion of fibroblasts. We discovered that overexpression of TGFB1 in ECs of mice significantly increased atrial fibrosis, and thus prolonging AF duration. Besides, knockout of TGFB1 in ECs of mice underwent TAC significantly attenuated the atrial fibrosis and decreased the rate of AF. Conclusion Our work demonstrates that mesenchymal ECs-derived Tgfb1 plays an important role in atrial remodeling by regulating the fibroblast function. EC-specific interventions were suggested to facilitate the development of novel strategies for mitigating AF substrate remodeling.

Role of 3D-electro-anatomical mapping on procedural characteristics and outcomes in pulsed-field ablation for atrial fibrillation

Abstract Introduction While the utilization of dedicated 3D-electro-anatomical mapping (EAM) systems for catheter ablation of atrial fibrillation (AF) is crucial using radiofrequency, its potential benefits in pulsed-field ablation (PFA) remain uncertain. This is of particular interest, since some PFA ablation systems will soon be available with integrated 3D-EAM capabilities. Objectives To compare the procedural characteristics and outcomes of patients undergoing PFA for pulmonary vein isolation (PVI) with mapping and with no mapping. Methods We prospectively enrolled patients undergoing their first PVI at a tertary referral center. In patients undergoing PVI with mapping, a multipolar mapping catheter was used to create voltage maps during sinus rhythm pre- and post-ablation. In the non-mapping group PVI was confirmed by assessing entrance block via the PFA catheter. The first 30 cases with mapping were excluded to account for a potential learning curve. Results A total of 197 consecutive patients were included (age 65 [interquartile range (IQR) 58 – 72] years; indexed left atrial volume 40 [IQR 35 – 44] mL/m2). Among these, 127 patients (64%) underwent PVI with mapping and 70 patients (36%) with no mapping. The median procedure duration, left atrial dwell time and the fluoroscopic time for the mapping vs the non-mapping group were 55 [IQR 45 – 67] min vs. 28 [IQR 23 – 35] min (p < 0.001), 38 [IQR 30 – 49] min vs. 15 [IQR 11 – 21] min (p < 0.001), 11 [IQR 9 – 14] min vs. 8 [IQR 7 – 11] min (p < 0.001), respectively. In the mapping group in 9% (11/127 patients) at least 1 PV was incompletely isolated and required additional applications. Acute PVI success was 100%. There were two complications in the mapping group (one stroke, one coronary artery air embolism) and none were observed in the non-mapping group. The recurrence rate of atrial arrythmias during a median follow-up of 267 [IQR 164 – 419] days was 14% in the mapping group and 17% in the non-mapping group, p = 0.728. Conclusion In conclusion, the use of PFA with no mapping was associated with a significant decrease in procedural characteristics, while AF-recurrence was not significantly different. The routine use of mapping for PFA-PVI may not be needed.Figure 1

Impact of atrial fibrillation on cardiac autonomic function in elderly patients

Abstract Introduction Cardiac autonomic dysfunction has been linked to an increased risk of mortality (1), stroke and silent brain lesions (2) and cognitive impairment (3) in patients with atrial fibrillation (AF). However, the impact of AF on cardiac autonomic function is poorly understood. Purpose We aimed to explore the impact of AF on cardiac autonomic function by comparing AF patients with a matched control cohort without AF. Methods We enrolled patients with and without AF from two ongoing, prospective, multicenter cohort studies (Swiss-AF Cohort and Swiss-AF Control) if they had a high-resolution 16-lead resting ECG recording in sinus rhythm for a duration of 5 minutes at baseline visit. Cardiac autonomic function was quantified by periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity. PRD was quantified by means of wavelet analysis, as validated previously (4). Cardiac autonomic dysfunction was defined present if PRD exceeded the established cut-off of 10.0 deg2 (5). We built multivariable adjusted linear and logistic regression models to explore the association of AF with PRD and cardiac autonomic dysfunction. Results We included 2077 patients, 1113 (54%) from the AF cohort and 964 (46%) from the matched non-AF cohort. Baseline characteristics were well balanced between the groups (mean age 71 vs. 73 years in patients with and without AF, mean CHA2DS2-VASc score 3.0 vs. 3.5, female sex 31.3% vs. 36.6%). The median PRD was 18.2 deg2 (IQR 9.9-25.4) in patients with AF and 15.8 deg2 (IQR 8.1 -23.0) in patients without AF (p<0.001, Figure). 832 (75%) of the AF patients suffered from cardiac autonomic dysfunction, vs. 656 (68%) of the non-AF patients (p<0.001). Multivariable adjusted linear regression analysis revealed an independent association of AF with continuous levels of PRD (beta-coefficient -1.57, 95% CI -2.64 - -0.488, p=0.004). Further, AF was independently associated with the presence of cardiac autonomic dysfunction (Odds Ratio 1.48, 95% CI 1.18-1.87, p<0.001, Table). Conclusion In this cross-sectional analysis of a patient population with and without AF, AF was independently associated with increased PRD values, reflecting sympathetic predominance, and with the presence of cardiac autonomic dysfunction. These findings implicate a relevant role of AF in the development of cardiac autonomic dysfunction in elderly patients.Figure

Catheter ablation vs medical management for atrial fibrillation in patients with heart failure: a systematic review and metanalysis

Abstract Background Current guidelines recommend a class IIa recommendation for catheter ablation in Atrial Fibrillation [AFIB]. Traditionally, catheter ablation has been known to be more effective in maintaining sinus rhythm than pharmacological management. However, there is sparse evidence to suggest that this translates to improved clinical outcomes in patients with heart failure. We did a systematic review and meta-analysis of randomized trials to compare the efficacy of ablation vs medical management for AFIB in heart failure. Methods A systematic search was conducted for randomized trials from inception to Jan 2024 for studies comparing the outcomes of catheter ablation vs medical management for AFIB in heart failure. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, heart failure hospitalizations, change in LV ejection fraction (LVEF), AF recurrence rate, 6-minute walk test (6MWT), change in MLHFQ scores and cerebrovascular events. Random-effects models were used to calculate the pooled incidence, mean difference (MD), and risk ratios (RRs) with 95% confidence intervals (CIs). Results A total of 10 RCTs with 2,348 patients were included in this study. Pulmonary vein isolation was the mainstay ablation strategy used. Compared with medical management, Ablation was associated with a significant reduction in all-cause mortality (RR- 0.61; 95% CI, 0.48-0.78; P<0.0001). Ablation was also associated with lower cardiovascular (CV) mortality (RR- 0.52; 95% CI, 0.36-0.75; P<0.0004), heart failure hospitalizations (RR- 0.67; 95% CI, 0.54-0.82; P<0.0001) and AF recurrence rate (RR- 0.43; 95% CI, 0.25-0.75; P<0.003). The study showed an improvement in LVEF (RR - 6.05; 95% CI, 3.35-8.75; P<0.0001), 6MWT (RR- 13.99; 95% CI, 4.18-23.81; P<0.005) and in MLHFQ score (RR -6.98; 95% CI, -12.03 to -1.93; P<0.007. There was a statistically significant difference between the 2 cohorts in the rates of cerebrovascular events (RR- 0.68; 95% CI, 0.35-1.30; P<0.24). Conclusion Randomized trials have shown clear benefits with catheter ablation compared to medical management for AFIB in heart failure. Ablation has demonstrated significantly lower all-cause mortality, reduced CV mortality, HF hospitalizations, AFIB recurrence rate, and improvement in LVEF. Patients who underwent catheter ablation showed improvement in functional outcomes like 6MWT and MLHFQ scores. There was no difference in the incidence of cerebrovascular events compared to medical management. This study adds to the growing evidence in the literature for ablation therapy; however, more trials are needed to identify patients for optimal benefits across the spectrum of heart failure patients.Forest PlotsForest Plots

The predictive value of left atrial functional parameters for recurrence of atrial fibrillation after catheter ablation in patients

Abstract Background Catheter ablation (CA) is a first-line treatment option for patients with symptomatic or drug-refractory atrial fibrillation (AF), yet the recurrence rate of AF post-CA remains considerably high. Studies have reported that left atrial (LA) functional parameters can serve as predictive factors for AF recurrence, however, the results remains controversial. Purpose This study aims to investigate the predictive value of LA functional parameters for AF recurrence following CA in patients. Methods We prospectively enrolled patients with AF who underwent CA for the first time from June 2022 to May 2023 and met the inclusion criteria at our institution. All patients underwent pre-ablation evaluation of LA structure and function, including LA diameter (LAD), LA maximum volume (LAVmax), LA minimum volume (LAVmin), LA pre-systolic volume (LAVpre), LA reservoir strain (LASr), LA strain conduit (LAScd), LA contraction strain (LASct), and LA ejection fraction (LAEF) using three-dimensional speckle tracking echocardiography. AF recurrence was defined as atrial tachycardia occurring 3 months after ablation and lasting longer than 30s. Patients were followed up for 9 months post-CA , and the primary end point was any atrial tachycardia occurring at 3 months after ablation. Results A total of 85 patients with AF were ultimately included in this study, with an average age of 68.9±11.0 years, 54.2% of whom were male. During the 9-month follow-up, 30 patients (35.29%) experienced recurrence postoperatively, while 55 patients (64.71%) still maintained sinus rhythm. Compared with the AF non-recurrence group, the AF recurrence group had significantly increased LAD (46.4±5.5mm vs. 42.3±4.5mm, p<0.05), LAVmax (80.7±21.3mL vs. 67.1±22.0mL, p<0.05), LAVmin (63.8±18.0mL vs. 42.8±16.9mL, p<0.05) and LAVpre (72.4±19.4mL vs. 53.9±16.8mL, p<0.05). Meanwhile, in AF recurrence group, LAEF (21.7±6.8% vs. 37.5±8.0%, p<0.05), LASr (5.1±3.1% vs. 12.0±5.4%, p<0.05), LAScd (-4.0±3.6% vs. -7.3±5.7%, p<0.05), and LASct (-1.0±3.8% vs. -3.3±4.9%, p<0.05) were significantly decreased. Multivariate logistic regression analysis revealed that LASr (OR=0.640, 95%CI 0.425-0.964, p<0.05) and LAEF (OR=0.816, 95%CI 0.694-0.960, p<0.05) were independent risk factors for predicting AF recurrence. ROC curve analysis showed that both LAEF (AUC=0.935, 95%CI 0.871-0.999) and LASr (AUC=0.903, 95%CI 0.833-0.973) possess high predictive values. Furthermore, the combined model of LAEF and LASr (AUC=0.954, 95%CI 0.905-1.000) had a greater predictive value than any one of the two indicators (p<0.05). Conclusion Taken together, these findings indicate that LAEF and LASr are independent predictors of AF recurrence following CA in patients with AF. Combination of the two indicators can more accurately assess the risk of recurrence in AF patients post-CA.

The prevalence and prognostic impact of low voltage zone in patients with cardiomyopathy after catheter ablation for atrial fibrillation

Abstract Background The low voltage zone (LVZ) in left atrium (LA) was observed in 20-30% of patients undergoing catheter ablation of atrial fibrillation (AF). Furthermore, LVZ was associated with not only AF recurrence but also prognosis. However, the prevalence and prognostic impact of LVZ in patients diagnosed with cardiomyopathy remained unclear. Purpose In this study, we focused on the patients with cardiomyopathy after AF ablation and investigated the prevalence and prognostic impact of LVZ after AF ablation. Methods This study is a single-center retrospective observational study. We enrolled 125 patients diagnosed with cardiomyopathy. All patients underwent voltage mapping after pulmonary vein isolation. LVZ was defined as regions where bipolar peak-to-peak voltage was <0.5mV. We set 5 cm² as the cutoff of the presence of LVZ. The etiology of cardiomyopathy was divided into arrhythmia-induced cardiomyopathy (AICM) and non-AICM consisting of idiopathic dilated cardiomyopathy (iDCM), hypertrophic cardiomyopathy (HCM), ischemic cardiomyopathy (ICM), transthyretin amyloidosis wild type (ATTRwt) and others (1 Fabry disease, 1 cardiac sarcoidosis, 1 restrictive cardiomyopathy). AICM was defined as patient whose LVEF was recovered above 50% after maintenance of sinus rhythm. We investigated the proportion of LVZ by etiology, and the association between LVZ and the composite endpoint consisting of all cause death, heart failure hospitalization, ventricular assisting device implantation, ventricular arrhythmia and stroke. Results Out of 125 patients [age 68 (58-73), female 32 (25%), LVEF 34.0 (25-43)], 51 (41%) had LVZ. Sixty-four patients were AICM etiology (LVEF pre to post: 30.7±10.7% to 61.1±6.7% ) and 61 was Non-AICM etiology (LVEF: 40.7 ± 18.1 to 44.7±15.7, P=0.0062). The presence of LVZ was lower in AICM than in non-AICM group (20.3% vs. 62.3%, P<0.0001). The etiology of non-AICM was consisting of 26 iDCM, 18 HCM, 7 ICM, 7 ATRRwt and 3 other etiology. The prevalence of LVZ was lower in AICM than in non-AICM (20.3 vs. 62.3%, P<0.0001). Detail is shown in Figure 1. Next, the incidence of composite endpoint was higher in patients with LVZ than in those without (HR 4.6, 95%CI 2.1-10.0, P=0.0001) (Figure 2A). Among 4 groups stratified by AICM/non-AICM and with/without LVZ, there was significant difference in the incidence of the composite endpoint (Figure 2B, P<0.0001). After adjusted with age, gender, Non-AICM, LVZ, LVZ tended to have association with composite endpoint (2.21, 0.87-5.65, P=0.097) and Non-AICM showed strong association (5.58, 1.55-20.12, P=0.0086). LVZ was associated with HF hospitalization (4.35, 1.21-15.61, P=0.024). Conclusions The prevalence of LVZ was 60% in Non-AICM, while it was 20% in AICM. LVZ tended to be associated with poor prognosis of cardiomyopathy after AF ablation. LVZ was associated with HF hospitalization in patients with cardiomyopathy. LVZ might be the marker for poor prognosis in cardiomyopathy cohort.

Assessment of mechanical dyssynchrony can improve the new ESC-2021 guidelines for cardiac resynchronization therapy

Abstract Background In 2021, new guidelines for cardiac resynchronization therapy (CRT) were published by the European society of cardiology (ESC-2021), where the different classes of recommendations were based on a new ECG-based definition of left bundle branch block (LBBB). However, its association with reverse LV remodeling and additive prognostic value remain unknown. Aim To investigate (1) the association between the ESC-2021 CRT guidelines and reverse LV remodeling at follow up, and (2) the additive prognostic value of baseline assessment of mechanical dyssynchrony to the ESC-2021 guidelines. Methods We investigated 244 heart failure patients in sinus rhythm treated with CRT in two European centers. 70% of the population were males. Mean age was 69 ± 10 years, QRS duration: 154 ± 24 msec. Mechanical dyssynchrony at baseline was defined as the presence of apical rocking or septal flash (ApRock/SF) in 2D transthoracic echocardiography. LV volumes were measured at baseline and at 12 ± 6 months after CRT, where the amount of CRT induced reverse LV remodeling was calculated as the percent change of LVESV at follow-up compared to baseline. Results Applying the ESC-2021 LBBB definition, only 18% (n=45) of patients had LBBB. Applying the guidelines, only 14% (n=35) had class I recommendation (LBBB + QRS ≥ 150 msec), 44% (n=107) had class IIa (LBBB + QRS 130-149 msec or non-LBBB + QRS ≥ 150 msec), 29% (n=70) had class IIb (Non-LBBB + QRS 130-149 msec), and 13% (n = 33) were not recommended according to the ESC-2021 because of having baseline QRS duration between 120 and 129 msec. On the other hand, ApRock/SF was evident in 57% (n=140) of the patients. There was non-significant difference in the relative decrease in LVESV at follow up between patients with LBBB and non-LBBB applying the new LBBB definition (44% [IQR: 32-63], vs. 39%, IQR [20-57], P = 0.08, panel A). Similarly, there was no significant difference in the relative decrease in LVESV at CRT follow up among the four guideline recommendation classes, panel B. We combined presence of mechanical asynchrony at baseline with each of the guideline recommendation classes. The combination of ApRock/SF with classes IIa and IIb improved the prediction of reverse LV remodeling significantly (P<0.001 and <0.01 respectively), while adding mechanical asynchrony did not significantly improve prediction in the class I and the not-recommended subgroups. However, results of these last 2 may have been impacted by a small number of patients, panel C. Conclusion The new ESC-2021 definition of LBBB is associated with few patients with LBBB and consequently small number of patients with class I recommendation according to the new guidelines. There was weak association between the new ESC-2021 guideline classes of recommendation and reverse LV remodeling after CRT. However, baseline assessment of ApRock and SF can significantly improve the guidelines in predicting CRT outcome.

Strategy optimization for the combined procedure of left atrial appendage occlusion plus catheter ablation in patients with atrial fibrillation (COMBINATION): a multi-center, randomized study

Abstract Background The long-term efficacy and safety of combining left atrial appendage closure (LAAC) plus catheter ablation (CA) in patients with atrial fibrillation (AF) in a single procedure have been established. However, the optimal combining strategy has not been well elucidated. Objective To determine the impact of different combining strategies on long-term clinical outcomes. Methods In this prospective multicenter study, patients with non-valvular AF referred for the combining procedure were randomly assigned to the ablation-first or occlusion-first groups at a 1:1 ratio. We evaluated the outcomes of LAAC with a Watchman device and CA using a contact-force sensing catheter during long-term follow-up. Results Of the 202 randomized patients, 194(96.0%) completed the trial with 97 patients in each group. Baseline characteristics were comparable between groups. All procedures were accomplished with acute successful LAAC and restoration of sinus rhythm. Incidences of periprocedural complications were similar. Higher chronic peri-device leak (PDL, 15.5% vs 5.2%, P=0.031) and device-related thrombus (DRT, 8.2% vs 1.0%, P=0.035) rates were observed in the ablation-first group. The event-free survival rate of the primary endpoint (composite of stroke/transient ischemic attack, thromboembolism, clinically-relevant bleeding, cardiovascular rehospitalization/death) was significantly higher in the occlusion-first group (83.5% vs 71.1%, log-rank P=0.036, HR 0.53, 95%CI 0.29-0.95) during a median 2.5-year follow-up. Patients with male gender and higher CHA2DS2-VASc score were at lower risk in the subgroup analysis. Long-term freedoms from AF (77.3% vs 63.5%, log-rank P=0.039) and atrial tachyarrhythmias (70.1% vs 55.7%, log-rank P=0.044) were higher in the occlusion-first group, respectively. Conclusions The occlusion-first approach is recommended for combined procedures where a plug-like device is implanted due to its superior long-term clinical benefits.Flowchart of the COMBINATION trialIncidences of primary endpoint

Elucidating the mechanism of rapid functional recovery following atrial fibrillation ablation in patients with left ventricular systolic dysfunction

Abstract Introduction Successful sinus rhythm restoration by catheter ablation (CA) of atrial fibrillation (AF) rapidly improves cardiac function in patients with left ventricular (LV) systolic dysfunction. However, the underlying mechanism of this recovery remains unknown. Purpose To elucidate the mechanism of the functional recovery after CA of AF and systolic dysfunction. Methods We retrospectively examined 4001 consecutive patients who underwent first-time CA of AF between 2012 and 2021 at our institution. Of them, 505 patients had baseline LV ejection fraction (LVEF) of <50%. Among them, we enrolled 454 patients who received electrocardiogram-gated contrast-enhanced 256-slice multi-detector computed tomography (MDCT) (Brilliance iCT, Philips Medical Systems, Cleveland, Ohio) both at baseline and 3 months after CA. Changes in LV measures, wall thickness, and LV mass were examined based on MDCT data. Results A reduction of LV end-systolic volume (LVESV) (from 71 ± 37 ml to 46 ± 34 ml, p <0.001) and improvement of LVEF (from 39 ± 9% to 62 ± 14%, p <0.001) were observed after CA. However, there was no significant change in LV end-diastolic volume (LVEDV) (from 118 ± 49 ml to 116 ± 46 ml, p = 0.13). Mean wall thickness during diastole did not change (from 7.1 ± 1.4 mm to 7.1 ± 1.4 mm, p = 0.94), either. However, wall thickness during systole significantly changed after CA (from 10.0 ± 1.7 mm to 12.7 ± 2.8 mm, p <0.001). As a result, there was no significant change in LV mass after CA (from 84.3 ± 28.7 g to 84.4 ± 28.1 g, p = 0.88). A regression analysis revealed a significant inverse correlation between the delta LVEF and delta LVESV (r = -0.59, p <0.001). However, the delta LVEF was not correlated with the delta LVEDV and delta LV mass. Conclusions The rapid improvement of LVEF after CA of AF was attributed to a decrease in the LVESV. Unchanged LV mass indicated that this functional recovery was solely a mechanical issue, without evidence of myocyte regression.

H558R: a common polymorphism may modify the efficacy and toxicity of flecainide in maintaining sinus rhythm; a cohort study

Abstract Background Certain mutations in the SCN5A gene alter the function of the type V voltage-gated cardiac sodium channel and the therapeutic effect of flecainide.(1) One such mutation, H558R, represents a polymorphism with a high prevalence associated with the development of atrial fibrillation (AF).(2–5) Purpose We aim to determine its relationship with the efficacy and adverse effects of flecainide, as well as describe for the first time its prevalence in a cohort of European patients with AF. Methods We conducted a cohort study collecting data through indirect methods, with the study being blinded to all parties involved except the statistician. Patients prescribed flecainide (dose of 100 mg/12 h) and followed up in our health area (n=450,000 people) between 2017 and 2021 were identified. A primary composite endpoint consisting of initial inefficacy and early toxicity and a secondary combined endpoint of toxicity or inefficacy during follow-up were predefined. Results Out of 104 patients who met the criteria and agreed to participate, 59 (56.4%) did not have the mutation (H558R-/-), 38 (36.5%) were heterozygous (H558R+/-), and 7 (6.7%) were homozygous (H558R+/+). This high prevalence in European patients with AF is significantly higher than that previously reported in healthy individuals (20.4% in Caucasians, 9.2% in Asians).(6) When compared with patients without the mutation, H558R+/- patients had a lower incidence of the primary endpoint (p=0.02, picture 1), with an absolute risk reduction (ARR) of -21.5% (95% confidence interval (CI): -38.4% to -4.6%) primarily due to a lower rate of initial inefficacy (ARR -18.35%, 95% CI: -1.37% to -35.3%), and a trend towards lower early toxicity (ARR -7.36; 95% CI: -19.9 to +5.2%). This difference remained in the multivariate analysis (p=0.03, table 1). Moreover, the H558R+/- genotype was associated with lower toxicity or inefficacy over an average follow-up of 492 days (p=0,04, picture 1), with a hazard ratio of 0.53 (95% CI: 0.27 to 0.999). Conclusions The H558R+/- mutation shows a marked prevalence in a selected sample of patients with AF. Its presence is clinically relevant both in terms of early efficacy or toxicity and during follow-up. If these results are confirmed, it may signify a step towards personalized treatment for patients with AF, not only from the standpoint of efficacy but also safety.Table 1.Picture 1.

Unipolar electroanatomical mapping outperforms bipolar voltage in detecting LGE areas in the left atrium

Abstract Introduction In atrial fibrillation (AF) management, understanding left atrial substrate is crucial. While both electroanatomical mapping (EAM) and late gadolinium enhancement MRI (LGE MRI) are reliable methods in assessing atrial substrate and are associated with the ablation outcome, recent findings have highlighted significant discrepancies between bipolar low voltage areas (LVA) in EAM and LGE areas. Objective Explore the relationship between LGE areas and unipolar LVAs by utilizing multipolar high-density (HD) mapping. Methods Nineteen patients scheduled for AF ablation underwent pre-ablation LGE-MRI. Left atrial (LA) segmentation was conducted using a convolutional neural network, which subsequently generated a 3D mesh integrating the LGE data. HD-EAM was performed in sinus rhythm for each patient, capturing at least 4000 points. The EAM map and LGE MRI mesh were co-registered. LVA areas were defined using voltage cut-offs of 0.5 mV for bipolar and 2.5 mV for unipolar measurements. Correspondence between LGE areas and LVAs on the anterior and posterior LA wall was analyzed. Results Both bipolar and unipolar LVA demonstrated high precision in detecting LGE areas (100% and 88% respectively). However, unipolar LVA exhibited a remarkable accuracy of 81% for detecting LGE areas specifically, whereas bipolar LVA displayed a significantly lower accuracy of 28%. These findings were consistent across the different atrial walls. Conclusion Incorporating unipolar voltage data into electroanatomical mapping in the atrium may bridge the observed gap between LGE areas and bipolar LVAs. Our findings highlight the significance of unipolar voltage in evaluating the left atrial substrate, potentially offering a more comprehensive insight into the different layers of atrial walls, and opening the door for new approaches in AF therapy.

Strategic timing- early and delayed catheter ablation in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia. AF catheter ablation (CA) is superior to antiarrhythmic drug (AAD) therapy in maintaining sinus rhythm. However, not much is known regarding the optimal timing of the ablation. Purpose This review aims to examine the evidence supporting both early and delayed ablation approaches, as well as explore their respective disadvantages. Methods We performed an electronic search in databases such as PubMed, ScienceDirect, Springer, Wiley Online Library, focusing on studies published from 2013 until 2022 and including both observational studies and randomized controlled trials (RCTs). Left atrial diameter and ejection fraction (EF) were assessed. The limit between early and delayed ablation was set to be 3 years, considering delayed CA studies with a diagnosis-to-ablation-time (DAT) of 3 years or more, and early CA studies with a DAT of less than 3 years. Included studies were selected according to our eligibility criteria: observational studies or RCTs that included patients with symptomatic paroxysmal or persistent AF that underwent ablation using either radiofrequency or cryoballoon approach or both approaches, studies that reported DAT, studies that included a follow-up period, studies that evaluated AF recurrence or AF burden. Studies that included a surgical ablation, a hybrid ablation approach, or ablation for arrhythmias other than AF were excluded. Results Ten studies were selected out of 1387 identified records. After a follow-up period of 1 year, the early ablation subgroup had a lower mean AF recurrence rate (31.1%) compared to that of the delayed ablation subgroup (37.7%) ( p<0.0004). The median AF recurrence rate in radiofrequency ablation group was (47.8%) in comparison to the AF recurrence rate in cryoablation group which was (27.4%) (p<0.0001). In studies that included paroxysmal AF patients exclusively, the AF recurrence rate was directly proportional to the DAT(R=0.95). Conclusion Our results demonstrate that DAT correlates with recurrence rate at 1 year following AF CA, the shorter the DAT the better the outcome especially in paroxysmal AF population.Prisma study selection flow diagramCorrelation between DAT-AF recurrence

Effect of selective renal denervation guided by renal nerve stimulation on atrial remodeling

Abstract Background The renal nerves play a crucial role in regulating blood pressure (BP), and the parasympathetic nervous has been confirmed as one of the components of the renal nerves, with close connections to the central solitary nucleus. Renal nerve stimulation (RNS) can activate not only the sympathetic nerves, leading to an elevation in BP, but also the parasympathetic nerves, resulting in a reduction in BP. Multiple clinical studies have demonstrated that compared to pulmonary vein isolation (PVI), renal denervation (RDN) combined with PVI significantly increased the likelihood of freedom from atrial fibrillation, but its mechanism remains unclear. Purpose Exploring the effects of renal sympathetic denervation and renal parasympathetic denervation on atrial neural remodeling and structural remodeling from a histological perspective of atrial myocardium. Methods 24 adult healthy Kunming dogs were randomly divided into three groups: (1) RNS-guided reduced BP response sites ablation (RRA group, n=8), (2) RNS-guided elevated BP response sites ablation (ERA group, n=8), and (3) RNS only, no ablation (RSC group, n=8). Left atrial samples were obtained after a 4-week follow-up period. Results Compared to the RSC group, the ERA group showed a significant decrease in tyrosine hydroxylase (TH), while the RRA group showed a significant decrease in choline acetyltransferase (CHAT) and muscarinic acetylcholine receptor 2 (CM2) (Fig. 1A-1C). Histological results indicated that compared to the RSC group, the ERA group exhibited orderly arrangement of myocardial cells, with a significant reduction in the degree of mitochondrial swelling and a decrease in average myocardial cell area. In contrast, the RRA group showed disordered arrangement of myocardial cells, with some myofibril dissolution, noticeable swelling of cell nuclei and mitochondria, and an increase in average myocardial cell area (Fig. 1D). Further evaluation of left atrial fibrosis degree revealed that compared to the RSC group, the ERA group showed a significant decrease in Collagen I, with a reduction in interstitial fibrosis degree, while the RRA group showed a significant increase in Collagen I expression, with an increase in myocardial interstitial fibrosis degree (Fig.2). Conclusion Renal sympathetic denervation can reduce atrial sympathetic nerve, improve atrial macrostructure, ultrastructure, and fibrosis levels, which may be one of the reasons why RDN combined with PVI is more effective in maintaining sinus rhythm compared to PVI. Renal parasympathetic denervation can decrease atrial parasympathetic nerve, leading to deterioration of atrial tissue structure and exacerbation of fibrosis. This emphasizes the importance of electrical stimulation guidance during the RDN procedure to avoid "side effects" caused by renal parasympathetic nerves ablation.Figure 1Figure 2