bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline demographic and clinical characteristics as predictors of adverse outcomes to improve management of patients with AF receiving edoxaban: a subanalysis of the ETNA-AF registry
Authors: Morrone D , Chao T , Chen C , Choi E , De Groot J , Kirchhof P , Pecen L , Tse H , Unverdorben M , De Caterina R
Published: November 2023

Background/Introduction

Atrial fibrillation (AF) is associated with substantial morbidity and mortality for patients, and significant burden for societal health and health economy. Even optimal oral anticoagulation and treatment of concomitant conditions leave an unacceptable remaining morbidity and mortality.

Aim

The purpose of this analysis was to identify clinical parameters associated with cardiovascular events in patients with AF receiving adequate anticoagulation.

Methods

The Global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF observational, non-interventional programme prospectively collects data on characteristics and clinical outcomes in patients treated with the direct oral factor Xa inhibitor edoxaban for stroke prevention in AF from Europe, Japan, and other Asian countries. A risk prediction model was built and evaluated for two dependent variables: composite endpoint 1, consisting of cardiovascular (CV) death, all stroke or systemic embolism or transient ischaemic attack (TIA), myocardial infarction (MI), and venous thromboembolism (VTE); and composite endpoint 2, consisting of CV death, all stroke, and MI. Independent variables used to identify predictors of the composite endpoints included the following parameters at baseline: age, history of any stroke/TIA, peripheral arterial disease (PAD), heart failure (HF), coronary artery disease (CAD), major or clinically relevant non-major gastrointestinal bleeding, chronic obstructive pulmonary disease, body mass index <18.5 kg/m2, weight, creatinine clearance (CrCl), history of valvular disease, history of diabetes mellitus, smoking history, age ≥85 years, and hepatic impairment. Multivariable Cox analysis with stepwise selection was used to identify baseline predictors of the composite endpoints.

Results

Overall, 26,580 edoxaban patients were included in the analysis. At baseline, 3034 (11.4%) patients were ≥85 years. Additional baseline demographics and clinical characteristics are reported in Table 1. All clinical variables were significant predictors (P <0.05) of both composite endpoints. Stronger predictors of composite endpoint 1 included history of any stroke/TIA, PAD, HF, higher weight, and lower CrCl (all P <0.0001; Figure 1). Most significant predictors of composite endpoint 2 included a history of ischaemic stroke, PAD, HF, and weight (P <0.0001; Figure 1).

Conclusion

A history of ischemic stroke, peripheral artery disease, heart failure, and weight identify patients with atrial fibrillation at risk of cardiovascular events on optimal current therapy. These patients may benefit from targeted interventions including early rhythm control and intensified, integrated management. Additional external validation will be performed to further the additive value of the analysis presented here.Table 1Figure 1
Persistence to edoxaban treatment in patients with atrial fibrillation: Analysis from the Global ETNA-AF program
Authors: Diemberger I , Chen C , Choi J , De Groot J , Kirchhof P , Pecen L , Unverdorben M , Wang C , Yamashita T , De Caterina R
Published: November 2023

Background/Introduction

Direct oral anticoagulants (DOACs) are now the standard treatment for stroke prevention in most patients with atrial fibrillation (AF). However, many studies have reported suboptimal adherence and persistence to DOAC treatment. Data collected in routine care, such as in the Global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF program, may provide insight into factors associated with treatment persistence.

Purpose

Evaluate the persistence to edoxaban treatment in a large, unselected, real-world population using 2-year data from the Global ETNA-AF study.

Methods

The Global ETNA-AF program is a predefined integration of prospective, observational, non-interventional regional studies from Europe, Japan, and other Asian countries to evaluate the safety and effectiveness of edoxaban in patients with AF. Demographic and clinical characteristics were collected at baseline. In this analysis, patients were stratified by persistence to edoxaban treatment during a 2-year follow-up period (ie, persistence [PERS], suspension [SUS], permanent discontinuation [PERD], and suspension with later permanent discontinuation [SUS+PERD]).

Results

Overall persistence was high, with 87.1% of patients under edoxaban treatment at 2 years considering both groups that discontinued edoxaban at any time (PERD and SUS+PERD). Mean patient age, creatinine clearance, CHA2DS2-VASc, and HAS-BLED score were similar between the PERS (n = 20,053), SUS (n = 3088), PERD (n = 2936), and SUS+PERD (n = 503) groups (Table). In the PERS group, there were slightly fewer patients who received previous anticoagulation (vitamin K antagonist or DOAC) and were concomitantly using anti-platelet drugs at baseline. A larger proportion of SUS+PERD vs all other patients had a history of ischaemic stroke and/or major bleeding. Overall mortality was lower in patients in the PERS and SUS groups (0.79% [95% confidence interval {CI} 0.70–0.89] and 1.85% [95% CI 1.53–2.24], respectively) compared with patients who discontinued the treatment (PERD: 22.50% [95% CI 21.12–23.98]; SUS+PERD: 13.05% [95% CI 10.73–15.88]). Notably, persistence in the Global ETNA-AF program was generally higher than reported in GLORIA-AF at 2 years (70.9%) and XANTUS at 1 year (77.4%), despite a more compromised health profile especially considering the advanced patient age.

Conclusions

Treatment with edoxaban in routine clinical practice is associated with high persistence (87%) at 2 years in elderly patients with AF and multiple comorbidities. Persistence to edoxaban treatment was associated with better survival during the 2-year follow-up period. Further investigation is ongoing to determine the specific causes and consequences of edoxaban suspension and discontinuation to improve personalization of thromboembolic prophylaxis in patients with AF.Table 1
Has the use of concomitant cardiac medications improved over time in primary prevention ICD patients? Insights from the APPRAISE ATP study
Authors: Mont L , Daubert J , Kutyifa V , Zareba W , Ando K , Wold N , Yong P , Schuger C
Published: November 2023

Introduction

Patients (pts) implanted with an ICD for a primary prevention (PP) typically receive concomitant medications (meds) to treat LV dysfunction. However, It is not well established whether compliance with guideline-directed medical therapy (GDMT) has improved over time in this population.

Methods

Data were drawn from the MADIT-RIT (2009-2012) and APPRAISE ATP (2016-present) studies. Both studies were global in scope and enrolled pts who were implanted with an ICD for PP indications. Meds prescribed at baseline were compared between the two studies. Meds of interest included: evidence-based beta blockers [(BB-EV) defined as carvedilol, metoprolol, and bisoprolol], ACE inhibitors, ARBs, ARNIs, and mineralocorticoid receptor antagonists (MRA). SGLT2i were introduced into GDMT after the study APPRAISE ATP started and were not included. Meds were analyzed both individually and in combination as GDMT, defined as joint use of BB-EV, ACE/ARB/ARNI, and MRA. Differences were compared with a t-test for continuous variables, a Chi-square test for categorical data and a Cochran-Armitage trend test for ordinal categorical data.

Results

Demographics for the two studies were compared for pts who received ICDs in MADIT-RIT (n=742) and APPRAISE ATP (n=2627 enrolled with n=2596 randomized) and are shown in the table below. When compared to MADIT-RIT, APPRAISE ATP pts were significantly older with a greater prevalence of diabetes. Comparison of baseline meds are shown in both the table and in the figure. Although BB-EV and ACE/ARB use was slightly but significantly lower in APPRAISE ATP, these declines were offset by a significant increase in MRA use in APPRAISE ATP. A marked shift was seen over time with significant decline in use of ACE-I that was matched by a significant increase in use of ARBs, either alone or in combination with ARNIs. When considering meds used in combination for GDMT, pts in APPRAISE ATP were significantly more likely to meet GDMT recommendations than pts who were enrolled in MADIT-RIT (36.7% vs 27.2%, respectively, p<0.001).

Conclusions

In the APPRAISE ATP study, compliance with GDMT in PP ICD pts has significantly improved when compared to the MADIT-RIT study conducted 10 years previously. These changes have been characterized by greater use of MRAs as well as a shift away from ACE inhibitors towards use of ARBs and ARNIs. Although there was considerably greater compliance with GDMT, with approximately one third of pts fulfilling GMDT, opportunities still remain for improvement. Further investigation is needed to determine what influence greater compliance with GDMT may have on improved clinical outcomes such as reductions in VT/VF event rates and all-cause mortality.
Left atrial functional changes and its predictive value in the early period after cryoballoon ablation for paroxysmal atrial fibrillation
Authors: Soysal A , Golcuk E , Ozturk S , Atici A , Gulfidan A , Yalman H , Ceviker A , Tokdil H , Raimoglu U , Cimci M , Durmaz E , Ikitimur B , Yalin K
Published: November 2023

Introduction/Purpose

In patients with paroxysmal atrial fibrillation (PAF), functional changes are observed in the left atrium (LA) after the pulmonary vein isolation (PVI) procedure. Although previous studies have investigated the altered mechanical functions of the LA with radiofrequency (RF) ablation, changes in the LA functions in the early period after cryoablation (CB-2) and the relationship between early period serial echocardiographic follow-ups after cryoablation and recurrence of atrial fibrillation/atrial tachycardia (AF/AT) have not been clearly demonstrated. This study aims to determine changes in the mechanical functions of LA in patients with PAF during the early period after cryoablation and whether these changes are effective in predicting the risk of recurrence by using echocardiographic parameters including Doppler and strain parameters.

Methods

Consecutive seventy-seven patients (mean age: 57.5±11.2 years; 57% men) with PAF underwent CB-2 and were prospectively analyzed. All patients were in sinus rhythm before and after the procedure. The LA dimensions, the LA reservoir strain (LASr), the LA atrial contractile strain (LASct), the LA conduit strain (LAScd) and left ventricular diastolic function parameters were evaluated by Doppler echocardiography before and 3 months after the procedure. Patients were monitored with 48-hour Holter at 1-3-6-12th months after the procedure to evaluate for recurrence.

Results

Acute procedural success was achieved in all cases. No major complications were observed. LASr and LASct showed significant recovery after the procedure (28.3±12.8% vs 34.6±13.8%, p<0.001 and -10.8±7.9% vs -13.9±9.3%, p=0.014 respectively). No significant change was demonstrated in other echocardiographic parameters. During the one-year follow-up after the procedure late recurrence (>3 months) of AF/AT was observed in 9 (11.7%) patients. Although the power of echocardiographic parameters in predicting recurrence was found to be not statistically significant, a downward trend especially in the values of LASr (p=0.068) and LASct (p=0.058) was observed at the 3rd month control echocardiographic results in patients with recurrence.

Conclusion

Significant improvement in mechanical functions may occur even in the early period after cryoballoon ablation in patients with PAF. In addition, as our study points out strain parameters, indicators of mechanical function tend to decline in patients with late term recurrence.
Comparison of ultralow temperature cryoablation and classical cryoballoon ablation for pulmonary vein isolation in patients with atrial fibrillation
Authors: Rudolph I , Bohnen J , Siebermair J , Rattka M , Rassaf T , Wakili R
Published: November 2023

Introduction

Pulmonary vein isolation (PVI) has become the standard-of-care in the treatment of atrial fibrillation (AF). In cryoablation cell damage is caused by freezing using predominantly nitrous oxide gas allowing temperature drops down to -60°C usually using a cryoballoon-based catheter (CB). Ultralow temperature cryoablation (ULTC) represents a novel ablation technique promising higher efficacy rates by achieving better transmurality of generated lesions. By using Nitrogen near it’s liquid vapor critical point (Near-critical nitrogen) in a linear catheter, ULTC achieves cooling temperatures as low as -196 °C. First studies using ULTC for PVI reported promising success rates. However, to date there is only limited data on outcomes of patients undergoing cryoablation with ULTC compared to CB.

Material and Methods

Our study aimed to compare the efficacy and safety of CB and ULTC ablation for PVI in AF patients. 90 consecutive patients with AF undergoing PVI by cryoablation at our university hospital between July 2020 and November 2022 were included in the analysis. The primary outcome was freedom from atrial arrythmia after 12 months. Furthermore, procedural parameters and periprocedural complications were compared.

Results

In total 90 patients, n=72 treated by CB ablation and n=18 by ULTC, were included in our study. Median age was 64yrs in CB and 70yrs in ULTC patients. Majority of patients of the CB (64%) and of the ULTC group (72%) were male. Paroxysmal AF was present in 57% of CB and 55% in the ULTC group. Median follow up was 365d for the CB and 232d for the ULTC group, respectively. The primary endpoint (Atrial arrythmia recurrence) occurred in 24/72 patients in the CB and in 10/18 patients in the ULCT group (HR: 0.47; 95% CI: 0.19-1.16; p=0.037).

There were no differences in periprocedural complications (CB: 12,5% vs. ULCA: 17%). Analysis of procedural parameters showed that the total procedure time was longer in the ULTC group (CB: 135 [124, 167] min, ULTC: 198 [168, 242] min; p=<0.0001). Fluoroscopy time was increased (CB: 23 min [16, 28] min, ULTC: 44 [38, 48] min; p=<0.0001) as was the median number of required freezes per vein in the ULTC group (ULTC: 4 [3, 6] vs CB: 1 [1, 2], p=< 0.0001).

Conclusion

The findings of this retrospective analysis comparing cryoablation by ULTC vs. CB for PVI in AF patients suggests that ULTC is not yet equivalent to CB ablation with respect to procedural parameters and freedom from AF. Nevertheless, learning curve and limited device handling experience has to be taken into account. Future controlled studies and randomized trials are required to further elucidate the value of ULTC in AF ablation procedures, especially in the context of the novel Pulsed field ablation technology.
Optimal cutoff duration of history or persistence of atrial fibrillation to undergo radiofrequency catheter ablation of longstanding atrial fibrillation
Authors: Matsunaga Y , Egami Y , Ukita K , Yasumoto K , Okamoto N , Yano M , Tanaka N , Masuda M , Watanabe T , Inoue K , Sunaga A , Hikoso S , Sakata Y , Nishino M , Tanouchi J
Published: November 2023

Background

The limitations of catheter ablation for longstanding atrial fibrillation (LsAF) are beginning to emerge and appropriate patient selection are needed. It is well known that the longer the duration of atrial fibrillation (AF), the less likely it is to be cured by catheter ablation.

Purpose

To identify the optimal cutoff duration of AF to predict outcomes after catheter ablation in patients with LsAF in the contact force sensing catheter (CF) era.

Methods

From the EARNEST-PVI (Effect of Extensive Ablation on Recurrence in Patients with Persistent AF Treated with Pulmonary Vein Isolation) trial, which was a prospective, multicenter, randomized, open-label trial, comparing the pulmonary vein isolation (PVI) alone and PVI plus additional substrate ablation, factors associated with arrhythmia-free survival after a 3-month blank period were evaluated in patients with LsAF.

Results

Among 124 patients, CF was used in 114 (92%). Duration of AF history and persistence were related to recurrences. Other factors, including age, gender, left atrial diameter, chronic kidney disease and substrate ablation, were not related to recurrences (Table). Receiver operating characteristic analysis detected suitable cutoff duration of AF history and AD persistence as both 2.4 years (area under curve; 0.654 and 0.609, respectively)). The arrhythmia-free survival was significantly better in patients with AF history ≤ 2.4 years than the others (p=0.001, HR 2.69, 95% CI: 1.47-4.89) and better in patients with AF persistence ≤ 2.4 years than the others (p=0.008, HR 2.04, 95% CI: 1.19-3.48) (Figure).

Conclusion

Duration of AF history or persistence ≤ 2.4 years were suitable to undergo radiofrequency ablation of LsAF.TableFigure
Acute termination as an endpoint in individualised electrophysiological substrate ablation in persistent atrial fibrillation
Authors: Sharp A J , Gala A , Pope M T B , Betts T R
Published: November 2023

Background

Individualised electrophysiological substrate ablation in persistent atrial fibrillation (perAF) is complicated by the lack of a clearly defined procedural endpoint. The frequency of acute termination and its association with long-term outcomes is not well described.

Purpose

To define the frequency of acute termination with ablation in a cohort of patients with perAF undergoing catheter ablation with a non-contact charge density mapping (CDM) system and assess its correlation with long term outcomes.

Methods

The DISCOVER registry (NCT03893331) contains patients recruited to an ongoing multicenter, observational study of CDM guided endocardial ablation procedures. We searched the U.K. component of this registry for all patients presenting for perAF ablations to extract the necessary data for analysis.

Termination was considered secondary to ablation whether occurring directly from AF, or via an organized atrial tachycardia (AT). Follow up was performed at 6 and 12 months, and included patient reported recurrence, standard 12-lead ECG, and 7-day ambulatory ECG.

Results

Eighty-six patients were analysed. All presented in AF at the start of their procedure. Termination was with ablation in 18 (21%).

Six-month follow up data was available in 80 (93%), and 12-month in 71 (83%) patients. Freedom from AF was significantly higher in patients ablated to termination; at 6-months 82% vs 51% (p=0.02), at 12-months 69% vs 40% (p=0.04) [figure 1].

Rates of AT during follow up were similar between both groups; at 6-months 24% vs 25% (p=0.93), at 12-months 46% vs 33% (p=0.38) in ablation to termination vs no acute termination groups respectively.

Conclusion

Occurring in approximately 1/5th of our cohort, the value of ablation to termination as a marker of procedural endpoint may be limited; however, it is a predictor of favorable outcomes. Furthermore, there is no indication from our analysis of a hypothetical association with larger volumes of substrate modification and subsequently development of AT.Freedom from AF at 6 and 12 months
High-density open window mapping vs conventional mapping in accessory pathways ablation
Authors: Martinez Sande J L , Minguito-Carazo C , Gonzalez-Melchor L , Garcia-Seara J , Rodriguez-Manero M , Martinon-Martinez J , Garcia-Rodeja F , Jimenez-Ramos V , Fernandez-Lopez X A , Gonzalez-Ferrero T , Gonzalez-Juanatey J R
Published: November 2023

Background and purpose

High density (HD) mapping is associated with a reduction in fluoroscopy time compared to conventional mapping in accessory pathway (AP) ablation. The Open Window (OW) technique (CARTO 3, Biosense Webster) is a new tool that automatically uses conventional electrophysiology criteria for AP location, as shorter local EGM AV interval (extended early meets late tool), earliest local activation time (LAT) and annotation at unipolar signal (wavefront annotation). However, no studies comparing its feasibility to conventional mapping have been conducted. Therefore, the aim of the present study was to assess the feasibility and the clinical implications of high-density OW mapping when compared to conventional HD mapping.

Methods

A prospective, unicentric cohort study was conducted that included consecutive patients which were referred to our institution for AP ablation with OW mapping technique and compared to a recent retrospective cohort of patients who underwent conventional HD mapping. Total fluoroscopy time, total mapping time and the rate of recurrence of the AP were compared between groups. A schematic step by step graphic of the workflow procedure is represented in figure 1.

Results

A total of 33 consecutive patients (32.28 ± 18 years, 58% males) were included in the OW group and compared with a cohort of 29 patients (29.6 ± 18 years, 52% males) who underwent conventional HD mapping. An example of Right Superior AP ablation is showed in figure 2. No differences in the location of the AP were observed (p=NS). OW mapping was associated to a lower mapping time (29.3 vs 37.8 min; p=0.04), lower fluoroscopy time (14.3 vs 21.3 min; p= 0.04) and lower radiofrequency time (p=0.007). After a median follow up of6 months, there were no differences in the rate of recurrence of the AP conduction between groups (p=NS).

Conclusions

In our experience, OW mapping was a feasible tool for AP location associated to a lower mapping time, lower radiofrequency time and lower X-ray exposure time with no differences in recurrence rate when compared to conventional HD mapping. However, more studies should be performed to corroborate these conclusions.Step by Step WorkflowRight Superior AP ablation
Distribution of triggers in the left atrial posterior wall in AF patients undergoing catheter ablation
Authors: Mohanty S , La Fazia V M , Torlapati P G , Gianni C A R O L A , Macdonald B , Mayedo A , Della Rocca D G , Bassiouny M , Gallinghouse G J , Burkhardt J D , Horton R , Al-Ahmad A , Di Biase L , Natale A N D R E A
Published: November 2023

Introduction

Having a common embryologic origin with the pulmonary veins (PVs), left atrial posterior wall (LAPW) is considered to be a source of non-PV triggers that facilitate maintenance of atrial fibrillation (AF). However, the benefits of electrical isolation of the posterior wall (PWI) is still debated with contradictory data originating from different ablation approaches.

Purpose

We report the distribution of triggers in the LAPW area in AF patients undergoing repeat ablation.

Methods

Consecutive AF patients undergoing catheter ablation between 2015 and 2022 were included in this analysis.

PVs were isolated first. Next, high-dose isoproterenol challenge (up to 30µg/min) was used to disclose triggers in the PW by moving the circular mapping catheter along the PW down to the level of coronary sinus, which were targeted using additional RF energy. We defined lower part of LAPW as the area between the line joining the inferior borders of the inferior PV-encircling lesions and the coronary sinus. The endpoint was to achieve electrical isolation, as documented by absence of any electrical activity in the PW.

Results

Of the 10,963 AF ablations performed during the specified time period, 6249 (57%) had triggers mapped and ablated in the LAPW area.

Triggers were seen to be originating from the part of the PW between the PVs in 4124 (66%) and from the lower part of the PW in 2125 (34%) patients. Of these, 1624 (26%) patients had focal triggers detected in both the area between the PVs and the lower PW. All triggers from in between PVs were targeted for ablation, whereas lower PW sites were ablated in 1296 (61%) and not targeted for ablation the remaining 829 (39%). Figure 1 demonstrates the triggers arising from lower PW.

At 1 year, amongst patients with lower PW triggers, 1049/1296 (81%) vs 326/829 (39.3%) (p<0.001) were arrhythmia-free.

Conclusion

Ectopic triggers in the LAPW were documented to be arising from the lower part of the PW in approximately 1/3rd of cases and ablation of those sites resulted in significantly higher success rate.
15-month follow-up of catheter ablation for atrial fibrillation in octogenarians
Authors: Wahedi R , Willems S , Jularic M , Hartmann J , Anwar O , Dickow J , Harloff T , Gunawardene M
Published: November 2023

Background

Catheter ablation for atrial fibrillation (AF) in octogenarians poses a challenge due to comorbidities, frailty, and suspected higher complication rates. Data regarding the outcome of catheter ablation in this population is scarce.

Purpose

Due to the projected increase of octogenarians presenting with AF in the future, we investigated the outcome of catheter ablation in this patient population.

Methods

We retrospectively analysed octogenarians with symptomatic AF undergoing catheter ablation in a single centre, including first and re-ablation procedures. Catheter ablation involved pulmonary vein isolation (PVI) using radiofrequency (RF), cryoballoon (CB) and pulsed field ablation (PFA) as energy sources and also atrial tachycardia (AT) ablation including linear lesions and/or ablation of complex fractionated atrial electrograms (CFAE). Follow-up (FU) was obtained to assess arrhythmia-free survival after a 90-day blanking period, recurrences after the blanking period, management of recurrences, rhythm at FU, use of antiarrhythmic drugs (AADs) and improvement in symptoms (EHRA symptom scale).

Results

A total of 126 patients (mean age 82.2 ± 1.9 years, paroxysmal AF n=48, persistent AF n=78, mean CHA2DS2-VASc-Score 4.2 ± 1.5) were included. 57.1% (n=72/126) underwent an index procedure {47.2% (n=34/72) RF PVI, 37.5% (n=27/72) CB PVI, 4.2% (n=3/72) PFA PVI and 11.1% (n=8/72) PVI + AT ablation}. 42.9% (n=54/126) received repeat procedures {20.4% (n=11/54) re-PVI, 42.6% (n=23/54) re-PVI + AT ablation, 37% (n=20/54) AT ablation}. FU of 108 patients after 15.4 ± 3.6 months revealed arrhythmia-free survival after the blanking period in 64.8% (n=70/108). Recurrence after the blanking period was seen in 35.2% (n=38/108). No significant difference in recurrences was shown between index and repeat procedures (32.3%, n=20/62 after index procedures and 36.7%, n=18/49 after repeat procedures, p =0.97). Management of recurrence involved repeat ablation (47%, n=18/38), AADs (16%, n=6/38), cardioversion (21%, n=8/38), pacemaker-implantation/AV-node ablation (5%, n=2/38) and pharmacological rate control (11%, n=4/38). At FU, 88.9% (n=96/108) of patients were in sinus rhythm with 21.3% (n=23/108) receiving AADs, 7.4% (n=8/108) were in AF, 0.9% (n=1/108) in AT and 2.8% (n=3/108) pacemaker-dependant. Symptoms were significantly improved at FU (mean EHRA score at FU= 1.2 ± 0.5, before ablation= 2.4 ± 0.5, p <0.0001).

Conclusion

Catheter ablation for AF in octogenarians is effective in maintaining sinus rhythm and controlling AF-related symptoms. Longer term success and impact on prognosis in this patient population is unknown and should be investigated further.
Transseptal puncture using electroanatomical mapping: a safe and cost-effective technique
Authors: Dantas Brigido A , Rassi G M , Rodrigues L V , Lovisi V B , Pisani C F , Chokr M O , Hardy C A , Melo S L , Goncalves A L M , Mayrink M P , Kulchetscki R M , Scanavacca M I
Published: November 2023

Background

The usual technique of transseptal puncture (TSP) uses fluoroscopy or intracardiac echocardiography. New techniques for oval fossa (OF) identification by electroanatomical mapping (EAM) have been described. However, the technique of direct visualization of the TSP needle added to the OF location by impedance mapping has not been investigated yet.

Purpose

To evaluate feasibility and safety of the TSP technique guided by the interatrial septum (IAS) impedance mapping and the TSP needle visualization using EAM system.

Methods

Consecutive patients who underwent ablation using TSP in July and August 2022 in our institute were included. The standard material for the procedure was used in addition to a temporary pacemaker (PM) connection cable. In all cases, the EAM system was CARTO 3 version 7 (Biosense Webster and a bipolar voltage map of right atrium and a impedance map of the IAS were constructed. The OF location was estimated based on the septal region with the lowest impedance and on traditional anatomical landmarks. Using a temporary PM cable connected to the proximal part of the TSP needle stylet, it was possible to visualize its distal portion on the 3D map used to guide the TSP. The entire process was simultaneously monitored under fluoroscopic visualization by an experienced professional.

Results

A total of 25 patients were included; mean age of 56 +/- 15 years, 16 (64%) were male. The most frequent procedure was atrial fibrillation ablation (86%); left atrium mean size of 40,26 +/- 5,2 mm. 9 patients (36%) were already submetted to a previous procedure using TSP. None of the patients had congenital heart disease. In all cases, the TSP was successfully performed and a correlation between the anatomical references and the lowest impedance region on the map was observed. There were no complications.

Conclusion

The technique of visualization of the TSP needle using EAM system added to IAS impedance mapping and use of anatomical markers seems to be a safe and cost-effective alternative for performing TSP. This technique could reduce ionizing radiation without need for additional materials.Impedance map and bipolar voltage mapLA (bipolar voltage map) and TSP orifice
Sex-differences in ventricular tachyarrhythmia events in patients with implantable cardioverter defibrillator and prior ventricular tachyarrhythmias
Authors: Krzowski B , Kutyifa V , Vloka M , Huang D T , Aktas M , Musat D , Rosenthal L , Sakaguchi S , Mcnitt S , Polonsky S , Schuger C , Daubert J P , Goldenberg I , Zareba W
Published: November 2023

Background

Women have been previously shown to be at a lower risk of ventricular tachyarrhythmia (VT) events in ICD trials, however, more contemporary data on the risk of VT/VF and death by sex in patients with prior VT/VF are lacking.

Objective

We aimed to assess sex-differences in ICD-treated VT/VF events and all-cause mortality in patients in the Ranolazine in High-Risk ICD Patients (RAID) trial. Patients were either implanted for secondary prevention or primary prevention ICD indications but experienced VT/VF before enrolment.

Methods

The RAID trial enrolled high-risk ICD patients with ischemic or non-ischemic cardiomyopathy, randomized to ranolazine or placebo. This analysis focused on patients with prior VT/VF. Sex-differences in VT/VF requiring ATP or shock were evaluated using Kaplan-Meier analysis, Fine and Grey, and Cox models in an intention to treat analysis. All VT/VF episodes were centrally adjudicated.

Results

There were 124 women (17%) out of 714 subjects analysed. Women were younger (60 vs. 65 years, p<0.001), more often non-ischemic (70% vs. 37%, p<0.001), less often had hypertension (69% vs. 78%, p=0.045) and diabetes (19% vs. 34%, p=0.002). Compared to men, women were at a significantly lower risk of VT/VF/Death (HR=0.67, [95% CI, 0.46-0.96], p=0.029), lower risk of VT/VF (HR=0.68, [95% CI, 0.46-1.00], p=0.049), lower risk of VT/VF treated with ATP (HR=0.59, [95% CI, 0.38-0.92], p=0.019), and lower risk of VT/VF treated with ICD shock (HR=0.54, [95% CI, 0.31-0.96], p=0.035). The risk of recurrent VT/VF was also significantly lower in woman (HR=0.35 [95% CI, 0.26-0.48], p<0.001). Hazard ratio for death was similar to the other endpoints, (HR=0.61, [95% CI 0.30-1.22] p=0.162) but did not reach statistical significance, most probably related to low statistical power due the relatively small number of death events among women. The effect of ranolazine on endpoints did not differ by sex.

Conclusions

Women with a history of prior VT/VF and managed with an ICD/CRT-D experienced a lower risk recurrent VT/VF requiring device therapy as compared with men. The risk of mortality showed a similar trend although did not reach significance.
Is there a significant 1-year impact on tricuspid valve regurgitation evolution in leadless-PM implanted subjects?
Authors: Sabatini A , Pellegrini N , Piccolo S , Capocci S , Strazzanti M , Tomasi L , Mugnai G , Franchi E , Tomei R , Ribichini F , Bolzan B
Published: November 2023

Background

Leadless pacemaker implanted subjects (leadless-VVI and "AV") have been shown to experience lower chronic complications and less device-related reinterventions compared to transvenous ventricular pacemakers (Transvenous-VVI, VDD) in the general PM-implanted-population. Also, conventional transvenous pacemaker ventricular leads may interfere with the tricuspid valve structures yielding significant tricuspid valve regurgitation (TR).

Purpose

This single-center study focusses on tricuspid valve disease to demonstrate the impact/benefits of leadless pacing at 1-year follow-up period by comparing tricuspid valve regurgitation grading at implant time and at 1-year follow-up.

Methods

This study is a retrospective, observational research study: 78 consecutive subjects (February 17, 2016 - January 18, 2023), treated in our Center, implanted with Micra VVI/AV leadless-PMs Micra MC1VR01 and Micra AVMC1AVR1, Medtronic, Inc., were evaluated at implant time via transthoracic echocardiography, and at 1-year follow-up period. Tricuspid valve disease was evaluated.

Results

See Table.

Conclusion

The main results from this study show that many patients at higher risk of transvenous pacemaker complications relatively to the tricuspid valve have similar tricuspid valve disease at implant time as compared to 1 year-F-up time, implicating a negligible impact of leadless pacing on the tricuspid valve compared to transvenous lead PMs.
Development of an in vitro platform for transesophageal echocardiographic and color Doppler hemodynamic assessments of left atrial appendage occlusion devices
Authors: Zhong Z , Ramon J , Morais P , Kandels T , Vij V , Nelles D , Nickenig G , Sedaghat A , Mela P
Published: November 2023

Introduction

Device-related thrombus (DRT) remains a significant complication after left atrial appendage occlusion (LAAO) and is associated with device position. Clinical prospective study of the influence of device position on DRT is cumbersome.

Purpose

To establish an in vitro bench test platform that allows visual, transesophageal echocardiographic and color Doppler hemodynamic assessments of left atrial appendage occlusion devices.

Methods

Based on a mock circulatory system, an in vitro platform was developed to create pathophysiological environment and left atrium wall motion under atrial fibrillation condition.

Results

LAAO devices could be visualized in the left atrium phantom model using transesophageal echocardiography and color Doppler measurement of local blood velocity at LAAO devices were proven to be capable. Deep implantations resulted in uncovered left upper pulmonary vein ridges. In comparison to ostium-fitted device positions, deep implantations were associated with reduced velocity of blood and the local velocity in the "cul-de-sac" remained lower than the critical threshold of 0.2 m/s.

Conclusions

An in vitro platform was developed that allows transesophageal echocardiographic and color Doppler hemodynamic assessments of left atrial appendage occlusion devices.
Risk of major cardiovascular events and bleeding in atrial fibrillation patients with chronic obstructive pulmonary disease treated with low dose azithromycin prophylaxis
Authors: Bucci T , Frost F , Wat D , Sibley S , Pignatelli P , Green D , Lip G Y H
Published: November 2023

Background

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events in patients with atrial fibrillation (AF). Low Dose Azithromycin Prophylaxis (LDAP) is associated with improved outcomes in people suffering frequent exacerbations of COPD, but the widespread use of macrolides in patients with underlying cardiovascular disease has been debated due to safety concerns.

Aims and Objectives

To investigate the safety and efficacy of LDAP in AF patients with COPD in a large global federated dataset.

Methods

We conducted a retrospective cohort study within the global TriNetX Platform, including AF patients with COPD exacerbations. Risks for all-cause death, major adverse cardiovascular events (MACE: acute coronary syndrome, thromboembolic events, severe ventricular arrhythmias, and heart failure), intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding were recorded up to 30 days post-COPD exacerbations and compared between LDAP users (at least 3 months use and using LDAP at index) and an active control group (non-Azithromycin users receiving inhaled corticosteroids (ICS)). Cox regression analyses compared outcomes between groups after propensity-score-matching (PSM) for cardiovascular risk factors.

Results

We identified 2791 LDAP users with COPD and AF (mean age 71.5±10.6 years, 48.9% female), and 61054 controls. Before PSM, LDAP users showed a lower prevalence of cardiovascular risk factors and were less likely to be prescribed oral anticoagulation (68.1% vs 76.1%, p<0.001). After PSM no significant baseline differences were found between two groups.

After COPD exacerbation, LDAP users were associated with a lower 30-day risk of all-cause death (HR: 0.72, 95%CI 0.60-0.97), MACE (HR 0.72, 95%CI 0.57-0.90), ICH (0.48, 95%CI 0.27-0.88) and GI bleeding (HR 0.69,95%CI 0.46-0.89) compared to the conventional treatment with ICS. Analysing the different time frames, the lower risk of thrombotic events was observed during the second week after COPD exacerbation while the magnitude of the bleeding risk reduction was more evident in the first 7 days (Figure 1).

Conclusion

LDAP use is associated with a lower risk of all-cause death, MACE and bleeding in AF patients with COPD. Further studies are needed to investigate the possible role of LDAP as part of the integrated care management of AF patients with COPD.
Changes in ubiquitylated proteins in atrial fibrillation associated with heart valve disease: proteomics in human left appendage tissue
Authors: Xiao Y , Wu C K , Teng S , Bai F , Liao X B , Zhou X M , Liu Q M , Zhou S H
Published: November 2023

Background

Posttranslational modifications have been shown to be associated with atrial fibrillation (AF). However, the relationship between ubiquitylated proteins and AF in patients with valvular heart disease remains unclear.

Purpose

To investigate the ubiquitination profiles in the left atrial appendage of patients with AF and valvular heart disease using LC-MS/MS analysis.

Methods

Eighteen subjects who underwent cardiac valvular surgery were included in this study, with nine in sinus rhythm and nine with AF. Ubiquitination profiles were analyzed using LC-MS/MS, and upregulated and downregulated ubiquitination sites were identified using quantification ratios.

Results

A total of 271 upregulated and 467 downregulated ubiquitination sites were identified in 162 and 156 proteins, respectively. The ubiquitylated proteins in AF were enriched in proteins associated with ribosomes, hypertrophic cardiomyopathy (HCM), glycolysis, and endocytosis. The study also revealed significant differences in the ubiquitination levels of ribosome-related and HCM-related proteins, including titin (TTN) and myosin heavy chain 6 (MYH6), between AF and sinus rhythm.

Conclusions

This study provides insights into the ubiquitination profiles in the left atrial appendage of patients with AF and valvular heart disease. Our findings suggest that ribosome-related and HCM-related proteins, especially TTN and MYH6, are differentially ubiquitinated in AF, which may provide a more feasible strategy against AF.Motif analysis of ubiquitylated proteinsUbiquitylated PPI network analysis
Clonal hematopoiesis of indeterminate potential in atrial fibrillation: prevalence and an association with progression
Authors: Ahn H J , Choi E K , An H Y , Lim J W , Koh Y , Choi S Y , Kwon S , Lee S R , Lip G Y H , Oh S
Published: November 2023

Background

Both clonal hematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. Also, CHIP is associated with an increased risk of cardiovascular disease which might contribute to the development of AF. However, the direct association between CHIP and AF is unknown.

Objective

To evaluate the potential role of CHIP in the development and progression of AF.

Methods

Deep-targeted sequencing of 24 CHIP mutations was performed in 1,004 patients with AF and 3,341 non-AF healthy adults. Variant allele fraction (VAF) ≥2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (1) the prevalence of CHIP mutations between AF and non-AF adults and (2) clinical characteristics discriminated by CHIP mutations within AF patients.

Results

The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. Twenty-four CHIP mutations with a VAF of at least 0.02 were found in 237 (23.6%) AF patients and 356 (10.7%) non-AF adults (p<0.001). The most common CHIP mutation genes in AF were DNMT3A (13.5%), TET2 (6.6%), and ASXL1 (1.5%). After multivariable adjustment, detected CHIP mutations were 1.4-fold higher in AF patients than in non-AF adults [odds ratio (OR), 1.38 and 95% confidence interval (CI), 1.10-1.73, p<0.01 for all AF; OR (95% CI), 1.50 (1.14-1.99), p<0.01 for long-standing persistent AF]. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (OR, 1.63; 95% CI, 1.03–2.56, p=0.036). AF patients with CHIP mutations were older and had more diabetes, a longer AF duration, and a higher E/E’ than those without CHIP mutations (all p<0.05).

Conclusion

CHIP mutations, primarily DNMT3A or TET2, are 1.4-fold more prevalent in AF than non-AF adults and might contribute to the progression of AF. Further studies are required to elucidate the underlying pathophysiologic role of CHIP in AF.
Differences in causality between exposures and stroke subtypes: a mendelian randomisation approach
Authors: Fill J , Fokina A , Klappacher G
Published: November 2023

Background

Observational evidence indicates that patients with atrial fibrillation (AF) are at a four- to fivefold increased risk of stroke. By two-sample mendelian randomization (MR), we have shown in our previous work that specifically the cardioembolic stroke subtype is caused by AF. This risk elevation is however variable and appears to be modulated by other risk factors such as hypertension traits and coronary artery disease (CAD).

Purpose

This study seeks to determine (1) whether genetic predisposition to cardioembolic stroke by AF is independent from modulators, and (2) whether the other stroke subtypes are causally linked with different exposures.

Methods

The associations between AF, hypertension traits, and CAD as exposures and stroke subtypes as outcomes were individually tested in a two-sample mendelian randomisation (MR) analysis using genetic instruments from publicly available genome-wide association studies (GWAS) in large cohorts. For atrial fibrillation, genetic instruments were obtained from the dataset by Nielsen et al. with 60,620 atrial fibrillation cases and 970,216 controls, collected from six contributing studies including the AFGen Consortium. Associations with stroke subtypes were evaluated in the MEGASTROKE genome-wide association study data set (67, 162 cases; 454, 450 controls). The genetic markers for hypertension traits were taken from a GWAS by Evangelou et al. which combines data from the UK Biobank (UKB) and the International Consortium of Blood Pressure (ICBP) with a total sample size of 757,601 individuals. Genetic instruments for CAD were obtained from the CARDIoGRAMplusC4D consortium (60,801 cases and 123,504 controls from 48 studies). Several MR regression methods such as MR-Egger regression and inverse-variance weighted regression as well as sensitivity analyses were applied. A multivariable MR model served to determine which of the exposures had an independent causal effect on each of the stroke subtypes.

Results

Atrial fibrillation turned out to be the sole independent causal risk factor for cardioembolic stroke with a beta coefficient of 0.75 (SE = ± 0.04; P = 8.59 x 10e-100) and an OR of 2.16 (1.97-2.27) in a multivariable model adjusted for AF, CAD, systolic blood pressure (SBP) and diastolic blood pressure. In this model, SBP and CAD were non-causative for cardioembolic stroke, but exhibited significant, albeit weak causal associations with small vessel stroke (SBP: OR 1.04 (1.02-1.06); CAD: OR 1.14 (1.02-1.28)) and large artery stroke (SBP: OR 1.09 (1.06-1.11); CAD: OR 1.59 (1.40-1.79).

Conclusions

Causality of the association between the cardioembolic stroke subtype and AF is independent from modulators such as SBP and CAD. However, SBP and CAD play a complementary role as causal exposures for small vessel and large artery stroke which in turn are not causally linked with AF.
Assessment of fibrosis in heart failure and atrial fibrillation using TIMP- 1 serum levels
Authors: Grosse A , Mettke F , Kirsch K , Gruen K , Franz M , Schulze P C , Surber R
Published: November 2023

Background

Tissue inhibitor of metalloproteinase- 1 (TIMP-1) levels are strongly associated with cardiac extracellular matrix accumulation and atrial fibrosis. The aim of this study was 1) to compare the TIMP-1 plasma levels in heart failure (HF) and atrial fibrillation (AF) patients and 2) to search for a local production in the heart.

Methods

This study included 13 patients with HF who underwent CRT implantation (CRT- group), 13 patients with persistent AF who underwent left atrial catheter ablation (AF- group) and 13 patients without structural heart disease or AF, who underwent electrophysiological study (control group). Blood was collected at the begin of the procedures from the coronary sinus (CS), superior vena cava (SVC) and aorta (Ao). Level of TIMP-1 in the CS (TIMP-1-CS), RA (TIMP-1-SVC) and aorta (TIMP-Ao) was measured.

Results

Patients characteristics: CRT- group: mean age 74y, 8 male, LV- EF 32%, 3 with a history of atrial fibrillation. AF- group: mean age 68y, 9 male, LV- EF 55%. Control- group: mean age 54y, 9 male, LV- EF 65%.

The levels of TIMP-1 in the SVC was in the CRT group significantly higher 213 ± 70 ng/ml vs 160 ± 23 ng/ml in controls (p= 0,03). The level of TIMP-1 in the AF- group (191 ± 73 ng/ml) was not significantly different from the control group (p= 0,195) (figure 1). At the various collection sites (CS, SVC and aorta), no significant differences between the 3 groups were noted.

Discussion: TIMP-1 serum levels in HF patients are significantly elevated compared to a control group without structural heart disease. No significant differences in levels of TIMP-1 were seen between AF patients and the control group. This is an expression of the advanced disease in the HF patients. The source of serum TIMP-1 are unclear as differences in the level of TIMP-1 between CS, SVC and aorta were not detectable.