bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of AT-02, a pan-amyloid-binding peptide fusion immunoglobulin with high binding potency, complement activation, and immune cell stimulation
Authors: Wall J S , Selvarajah S , Foster J S , Williams A , Richey T , Balachandran M , Jackson J , Hancock T , Stuckey A , Martin E B , Kennel S J
Published: November 2023

Background

Cardiac amyloidosis is an ominous manifestation of systemic amyloidosis, notably in AL and ATTR-associated types, resulting in a restrictive hypertrophic cardiomyopathy with electrical conduction and atrioventricular strain dysfunction (1). Amyloid is not naturally cleared by the immune system due to the presence of extracellular matrix components in the deposits (2). However, recruiting and stimulating the innate immune system, notably phagocytic macrophages, is a promising strategy to effect amyloid removal. To facilitate this, we have generated AT-02, a humanized IgG1 incorporating the pan-amyloid-binding peptide, p5R (3), at the light chain C-terminus. This reagent binds diverse types of amyloid via the peptide interactions and retains immunomodulatory capacity.

Purpose

The goal of these studies was to characterize the bioactivity of AT-02 that underlies its potential therapeutic activity.

Methods

AT-02 was produced from a CHO pool using a perfusion cell culture production process, purified by Protein A, anion exchange, and cation exchange chromatographies, and characterized by mass spectrometry and SDS-capillary electrophoresis. AT-02 was biotinylated and used for immunohistochemical detection of both AL and ATTR amyloidosis in formalin fixed tissues (Figure 1A). Binding to heparin (as a surrogate for amyloid-associated hypersulfated heparan sulfate proteoglycans) and synthetic AL fibrils was studied using both ELISA and surface plasmon resonance assays (Figure 1B). Activation of complement following binding to amyloid substrates was determined using a C5b9 liberation assay in the presence of human plasma. The effect of AT-02 on amyloid fibril growth was determined using a fluorescence fibril elongation assay. In vivo clearance of amyloid and cell activation was demonstrated using a murine model of AL amyloidoma.

Results

AT-02 bound human cardiac amyloid in tissue sections with high specificity and intensity. The potency for heparin and synthetic amyloid fibrils, as well as human cardiac amyloid extracts, was sub-nanomolar in the ELISA assay with kinetics consistent with a high affinity antibody. In the presence of plasma, complement activation of amyloid-bound AT-02 was significantly higher as compared to controls, and the reagent inhibited synthetic amyloid fibril growth by ∼40%. Treatment of human amyloid with AT-02 expedited phagocytosis by murine macrophages in vivo and enhanced the intensity of immune response to the implanted amyloid.

Conclusion

Clearance of cardiac amyloid is a significant clinical unmet need for patients with systemic amyloidosis. The humanized IgG1-peptide fusion, AT-02, potently binds cardiac amyloid and may serve as an opsonin and induce macrophage-mediated phagocytosis and clearance of cardiac amyloid deposits.
CAR-T cells inhibit vascular smooth muscle phenotypic switching and reduce intimal hyperplasia in vein grafts
Authors: Xiao B , Jiang Y , Guo Y
Published: November 2023

Background

Intimal hyperplasia (IH) is a prevalent cause of vein graft stenosis after coronary artery bypass grafting (CABG) in the middle and long term. Vascular smooth muscle cell (VSMC) phenotypic switching from a contractile phenotype to a synthetic phenotype is a hallmark of this process, along with the degradation of extracellular matrix (ECM) and smooth muscle migration. Chimeric antigen receptor (CAR)-T cell therapy is a targeted cellular immunotherapy that uses genetically engineered T cells to specifically eliminate the antigen-bearing cells. There is a potential to apply CAR-T therapy to cardiovascular diseases.

Purpose

In this study, we aim to design a novel CAR-T cell therapy to eliminate synthetic vascular smooth muscle cells in intimal hyperplasia, inhibit phenotypic switching, in order to reduce vein graft stenosis.

Methods and results

Using bulk RNA-seq dataset from the GEO database, we have identified human organic cation transporter (OCT1) as a key marker for synthetic vascular smooth muscle cell in vein grafts (Fig.1A, B). We then engineered switchable fourth-generation CAR-T cells incorporating CD28 and CD3 ζ costimulatory domains (Fig.1C, E). In addition, these CAR-T cells secrete tissue inhibitor of metalloproteinase-3 (TIMP3), a protein that had been shown to inhibit matrix metalloproteinases (MMPs) activity and the ERK1/2 pathway (Fig. 1F). Targeting FITC instead of OCT1 itself allows a controllable and switchable working process for the CAR-T cells, as they only start to identify synthetic VSMCs in combination with a FITC-conjugated OCT1 antibody (Fig.1D). Immunostaining of PDGF-induced synthetic VSMCs co-cultured with CAR-T cells and FITC-conjugated OCT1 antibody revealed increased expression of contractile markers, and reduced expression of synthetic markers (Fig1.G), along with decreased mitochondrial membrane potentials, which could be reverted after pre-treatment with a pan caspase inhibitor (Fig.1H),. In vivo studies using mice vein graft model showed reduced intimal thickness, increased intimal/medial ratio in cross-sections, in addition to increased peak velocity and inner wall diameter on ultrasound after CAR-T cell therapy (Fig.2).

Conclusion

Switchable CAR-T cell therapy targeting synthetic vascular smooth muscle cells might be a promising approach to alleviate intimal hyperplasia in vein graft stenosis.
Impact of sodium-glucose cotransporter-2 (SLGT2) inhibitors treatment initiation on the reduction of atrial and ventricular arrhythmias in patients with implanted cardiac devices
Authors: Minguito Carazo C , Sanchez Munoz E , Martinez Sande J L , Rodriguez Manero M , Fidalgo Andres M L , Garcia Seara J , Fernandez Lopez X A , Gonzalez Rebollo J M , Gonzalez Ferrero T , Rodriguez Santamarta M , Gonzalez Melchor L , Martinon Martinez J , Garcia Rodeja F , Fernandez Vazquez F , Gonzalez Juanatey J R
Published: November 2023

Introduction

Sodium-glucose cotransporter-2 (SLGT2) inhibitors have demonstrated benefits on survival and hospital admissions in patients with heart failure and reduced ejection fraction. However, their impact on the burden of ventricular (VA) and atrial arrhythmias (AA) is unknown.

Methods

Retrospective multicentric study of heart failure patients with implantable cardiac defibrillator device (ICD) from 2015 to 2020 with or without cardiac resynchronization therapy (CRT) receiving SGLT2 inhibitors. Device-registered arrhythmic events were analyzed and compared during one year following SLGT2 inhibitor initiation and during one year before initiation. Relevant VA were defined as the occurrence of any sustained VT (SVT) (>30 seconds), ventricular fibrillation (VF), or appropriate therapy (antytachycardia pacing or shock). All VA included all the relevant VA and the occurrence of non-sustained ventricular tachycardia (NSVT). AA included atrial fibrillation (AF) burden, and episodes of more than 24 hour of AF.

Results

147 patients (67 ± 10 years, 82.3% males, LVEF 30.3 ± 11%, CRT 39.3%), were included in the study. 77.6% had complete remote tele-monitoring during the entire follow up and there was no difference in the antiarrhythmic therapy between the two periods. Following SGLT2 inhibitor initiation, there was a significant reduction in the percentage of patients with relevant VA (19.7% pre vs 10.9% post; p=0.019) and all VA (47.6% pre vs 30.6% post; p<0.001) (Figure 1 and 2). There was a reduction in the prevalence of NSVT (40.1% pre vs. 27.2% post; p<0.001), of SVT (17.7% vs 8.8%; p<0.001), of VF (4.1% vs 2%; p=NS) and appropriate therapies (14.3% vs 9.5%; p=NS). Among patients with any VA, there was a significant reduction in the incidence of NSVT (p<0.001), but not in the incidence of SVT or appropriate therapies (p=NS). There was no impact on atrial fibrillation burden or in the number of AF episodes lasting more than 24 hours (p=NS).

Conclusions

In our study, initiation of a SGLT2 inhibitor in patients with heart failure, was associated with a reduction in the prevalence of relevant VA and any VA, with a significant reduction in the number of NSVT per patient. There was no impact on AF burden or the number of AF episodes lasting more than 24 hours. Prospective studies should be performed to sustain these conclusions.Relevant ventricular arrhythmiasAny ventricular arrhythmia
Cardiac resynchronization therapy with or without defibrillation in patients with non-ischemic cardiomyopathy: a systematic review and meta-analysis
Authors: Devesa Neto V , Ferraz Costa G , Ferreira Santos L , Teixeira R , Goncalves L
Published: November 2023

Introduction

Cardiac resynchronization treatment (CRT) is a significant medical achievement for patients with heart failure and electrical desynchrony to relieve symptoms, reduce hospitalization, and increase survival, both with and without implantable cardioverter-defibrillator therapy. However, the value of defibrillator therapy in addition to CRT in patients with non-ischemic cardiomyopathy (NICM) who are eligible for CRT remains unclear.

Objective

Compare the outcomes of patients with NICM and heart failure who received CRT with implantable cardioverter-defibrillator (CRT-D) against CRT-pacemaker only (CRT-P).

Methods

A literature search from inception through January 2023 was conducted in PubMed and Cochrane Central Register of Controlled Trials for all studies reporting outcomes of CRT-D versus CRT-P in CRT-eligible patients with NICM. Studies reporting non-stratified outcomes, including patients with ischemic cardiomyopathy, were excluded. The primary endpoint of interest was all-cause mortality. Secondary outcomes included device complications. A random-effects model was used.

Results

Of a total of 1976 potential citations, the search yielded 9 citations that met our inclusion criteria. Ten studies were included, one randomized clinical trial and nine observational studies, providing 11064 CRT-eligible patients with NICM (7459 CRT-D implantation and 1275 with CRT-P). Our meta-analysis revealed a significantly lower all-cause mortality (pooled OR, 0.85; 95% CI [0.75, 0.97], P = 0.02; I ²= 31%), albeit with moderate heterogeneity. Additionally, regarding device complications, only one study reported these outcomes with no significant difference (HR 0.82 [95% CI, 0.29–2.20]).

Conclusions

Our meta-analysis suggests that the addition of defibrillator therapy significantly reduced all-cause mortality in CRT-eligible patients with NICM.
Empirical Marshall vein ethanol infusion as the first-line strategy in patients with persistent atrial fibrillation undergoing mitral isthmus ablation
Authors: Du X F , Luo C X , Shen C J , Feng M J , He B , Fu G H , Wang B H , Liu J , Jin H , Gao F , Chu H M
Published: November 2023

Background

Marshall vein ethanol infusion (MVEI) as an additional therapy to conventional catheter ablation (CA) has been proved to be efficacious in patients with persistent atrial fibrillation (PeAF). However, whether empirical MVEI could be the first-line strategy in mitral isthmus (MI) ablation has seldomly been investigated.

Objective

To compare the efficacy, safety and long-term outcomes between provisional and empirical MVEI in PeAF patients undergoing their index MI ablation.

Methods

We enrolled 133 propensity-score matched patients with PeAF at a ratio of 1:2.5 either into the provisional group (n=38, MVEI was performed when conventional endocardial and/or epicardial ablations were inadequate to achieve bidirectional MI block) or the empirical group (n=95, MVEI was applied empirically before MI CA). Baseline characteristics, procedure results and long-term outcomes were compared between groups.

Results

All of the baseline characteristics were comparable. Less spontaneous or inducible atrial tachycardias (ATs) including MI-dependent ones were encountered in the empirical group (P<0.001). More epicardial ablations were applied (26.3% vs 9.5%, P=0.016) and higher incidence of CA-facilitated restoration of sinus rhythm was recorded (86.8% vs 11.7%, P<0.001) in the provisional group. Although more fluoroscopy time (6.4[4.2, 9.3] vs 9.5[5.9, 11.6] min, P=0.019) and radiation exposure (69.0[25.3, 160.2] vs 122.0[62.5, 234.1] mGy, P=0.010) were documented in the empirical group with comparable procedure time, less time was consumed to achieve bidirectional MI block during endocardial ablation in the empirical group (455.9±192.2 vs 366.5±161.3 sec, P=0.038). Incidences of procedure-related complications were similar between groups. During a 16.5±4.4-month follow-up, the empirical group showed significantly higher freedom from AT recurrence (81.6% vs 95.8%, log-rank P=0.003), while the freedoms from AF recurrence were similar. Both univariate (HR 0.19, 95%CI 0.05-0.64, P=0.008) and multivariate (HR 0.25, 95%CI 0.07-0.92, P=0.037) Cox regression analyses indicated that empirical MVEI was independently associated with lower long-term AT recurrence.

Conclusion

Among patients with PeAF underwent their index MI ablations, empirical MVEI could reduce the endocardial MI ablation time and improve the long-term freedom from AT recurrence.Flowchart of the study.Freedoms from AF and AT recurrence
Efficacy of nonocclusive separate freezing technique of cryoballoon pulmonary vein isolation: comparison of novel and conventional cryoballoon system
Authors: Arai H , Oda A , Murata K , Sagawa Y , Goya M , Sasano T , Yamauchi Y
Published: November 2023

Background/Introduction

Complete occlusion of pulmonary vein (PV) with cryoballoon is an important factor to achieve enough temperature drop and successful pulmonary vein isolation (PVI). However, it is sometimes difficult to occlude PV completely because of large diameter or anatomical difference. Distal cryoblloon positioning in the PV can achieve complete occlusion but it may increase risk of phrenic nerve injury or PV stenosis. Nonocclusive separate freezing technique, freezing superior and inferior portion of the PV at proximal side with no complete occlusion, may be useful for that situation but efficacy of the technique is not well elucidated.

Purpose

The purpose of this study is to investigate efficacy of nonocclusive separate freezing technique and compare procedure details of the POLARx and the Arctic Front Advance Pro (AFA-Pro).

Methods

We retrospectively analyzed consecutive patients who underwent cryoballoon ablation with nonocclusive separate freezing technique from September 2019 to February 2023. We defined failure of the nonocclusive separate freezing as the case which needed distal complete occlusion with cryoballoon or touch up radiofrequency ablation to achieve PVI. We analyzed success rate of nonocclusive separate freezing and evaluated nadir temperature, freezing time and number of application times. We also explored incidence of stop of freezing due to phrenic nerve injury (PNI) or esophageal temperature drop during the procedure and permanent PNI and gastroesophageal complications after the procedure between the POLARx and the AFA-Pro.

Results

One-hundred and one patients, 73 were male (72.3%) and mean age was 66.8 ± 10.5 years, were analyzed. Total PVs were 121 (left superior (LS) PV 31, right superior (RS) PV 53, left common (LC) PV 37) and the POLARx was 45 (LSPV 18, RSPV 24, LCPV 3) and the AFA-Pro was 76 (LSPV 13, RSPV 29, LCPV 34). Success rates of the separate freezing of the POLARx was 84.4% and the AFA-Pro was 77.6% (p=0.48). There were no significant differences in freezing time and number of application times but nadir temperature was significantly lower in the POLARx (-52.1 ± 4.7 °C vs -42.9 ± 7.2 °C, p<0.001). The incidence of stop of freezing had no significant difference between the POLARx and the AFA-Pro but nadir temperature of stop of freezing due to esophageal temperature drop was significantly lower in the POLARx (-53.8 ± 4.3 °C vs -44.7 ± 7.7 °C, p=0.039). Permanent PNI was not seen but two gastric hypomotility events occurred in the POLARx.

Conclusions

There was no significant difference of success rate of the nonocclusive separate freezing technique but it tended to be higher and nadir temperature was significantly lower in the POLARx. There was no obvious complication in the AFA-Pro but two gastric hypomotility events were seen in the POLARx.
The significance of excessive supraventricular ectopic activity immediately after catheter ablation in the risk stratification for late recurrence of atrial fibrillation
Authors: Fujisawa T , Kawakami H , Nagai T , Miyazaki S , Akazawa Y , Miyoshi T , Higaki A , Seike F , Higashi H , Nishimura K , Inoue K , Ikeda S , Yamaguchi O
Published: November 2023

Background/Introduction

Early recurrence of atrial fibrillation (AF) (<3 months) after ablation is associated with late recurrence (≥3 months). Even absent early AF recurrence, patients frequently experience postprocedural supraventricular ectopic complexes (SVEC). Excessive supraventricular ectopic activity (ESVEA) is a new surrogate marker for new-onset AF and poor stroke prognosis. However, the relationship between ESVEA and late recurrence of AF post-ablation is poorly understood.

Purpose

We hypothesized that postprocedural ESVEA would be associated with late recurrence of AF. We also investigated use of ESVEA compared to early recurrence of AF for stratifying patients’ risk of late recurrence of AF.

Methods

Participants were patients with AF who underwent initial radiofrequency catheter ablation and 24-Holter monitoring the day after the procedure between 2014 and 2020. SVEC was defined as supraventricular complexes occurring ≥30% earlier than expected compared with the previous RR interval. ESVEA was defined as at least 30 beats of SVEC per hour, or any episodes of SVEC runs ≥20 beats. Atrial tachyarrhythmia lasting for longer than the 30s was defined as AF recurrence. We analyzed the association between postprocedural Holter monitoring results and late recurrence of AF.

Results

We enrolled 469 patients with AF (average ± SD 63.6 ± 10.1 years; 32% female; 56% paroxysmal AF). We observed early recurrence of AF (n = 57; 12%) and ESVEA (n = 287; 61%) during postprocedural Holter monitoring in these patients; 125 patients (27%) had no signs of AF or ESVEA. During a median follow-up of 25 months, 152 patients (32%) experienced a late recurrence of AF. Patients who demonstrated early AF recurrence or ESVEA during Holter monitoring were significantly more likely to experience late recurrence of AF, even after adjusting for various clinical parameters and left atrial enlargement. Patients with early recurrence of AF had the worst outcomes, and AF-free survival was significantly worse in patients with ESVEA than patients without early recurrence of AF (Figure).

Conclusions

ESVEA on post-procedure day 1, even without AF, was associated with worse clinical outcomes following initial AF ablation. Postprocedural 24-Holter monitoring may reveal an increased risk of late recurrence of AF secondary to observation of recurrent AF or ESVEA.
Utilization and complications of atrial fibrillation catheter ablation among cancer patients
Authors: Margolis G , Goldhaber O , Kazatsker M , Roguin A , Leshem E
Published: November 2023

Background

Atrial fibrillation (AF) catheter ablation among cancer patients was evaluated only in a few small studies. We investigated the extent and in-hospital outcomes of AF catheter ablation procedures among cancer patients.

Methods

Using the National Inpatient Sample (NIS) database, patients who underwent AF catheter ablations in the US between 2016 and 2019 were identified using ICD-10 codes. Sociodemographic, clinical data, in-hospital procedures and outcomes as well as in-hospital mortality and length-of-stay (LOS) were collected. Baseline characteristics and in-hospital outcomes comparison between patients with and without cancer was performed.

Results

An estimated total of 36630 patients underwent AF catheter ablation between 2016-2019 in the US. Of them, 585 (1.6%) had cancer diagnosis. Compared with non-cancer patients, patients with cancer were older, had higherCharlson Comorbidity Index, as well as CHA2DS2-VASc and ATRIA bleeding indices scores (Table 1).

Higher rate of total complications was observed in cancer patients (10.3% vs 7.0 , p=0.002) driven mainly by more bleeding and infectious complications. LOS was also significantly longer in cancer patients (5.5 + 6.3 vs. 3.1 + 3.4 days, p<0.001). However, no significant differences in cardiac or neurological complications as well as in-hospital mortality rates were observed and were relatively low in both groups (Table 2).

Conclusion

AF catheter ablation in cancer patients is associated with higher bleeding and infectious complication rates, but not with increased cardiac complications or in-hospital mortality rates in a nationwide, all-comer registry.
Comparison in efficacy of catheter ablation for elderly versus non-elderly patients with persistent atrial fibrillation
Authors: Matsuoka Y , Sotomi Y , Hikoso S , Nakatani D , Okada K , Dohi T , Kida H , Sunaga A , Sato T , Kitamura T , Tanaka N , Masuda M , Watanabe T , Inoue K , Sakata Y
Published: November 2023

Background/Introduction

Atrial fibrillation (AF) is common arrythmia among elderly patients. Advancing age is reportedly associated with left atrium (LA) fibrosis and remodeling. We hypothesized that an extensive ablation strategy in addition to pulmonary vein isolation (PVI-plus) might be effective for elderly patients, whereas the PVI alone strategy (PVI-alone) might be sufficient for young patients to maintain sinus rhythm.

Purpose

We investigated the efficacy of ablation strategy (PVI-alone or PVI-plus) for AF patients stratified by age.

Methods

This study is a post-hoc analysis of the EARNEST-PVI trial. The EARNEST-PVI trial was a prospective, multicenter, randomized, and open-label non-inferiority trial comparing PVI-alone vs PVI-plus in patients with persistent AF. The primary endpoint was recurrence of AF.

Results

A total of 497 patients were eligible and divided into two groups (elderly group (age≥65, n=291) or young group (age<65, n=206)). In elderly group, the event rate was significantly lower in the PVI-plus group than in the PVI-alone group (Hazard ratio (HR): 0.587, 95% confidence interval (CI): 0.406 – 0.849, P = 0.0047), while the event rate was similar between both groups in young group (HR: 1.101, 95%CI: 0.687 - 1.77, P = 0.692) (P for interaction: 0.0411).

Conclusion

In elderly patients, PVI-plus strategy was more effective than PVI-alone, whereas the PVI alone strategy was sufficient for young patients.
Catheter ablation of persistent atrial fibrillation: circumferential pulmonary vein ablation with or without a linear lesion at the left atrial roof for (12-year follow-up)
Authors: Kettering K
Published: November 2023

Background

Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory atrial fibrillation. Circumferential pulmonary vein ablation is still the standard approach in these patients. However, the results are not very favourable and more complex ablation strategies are the subject of current controversy.

Therefore, we have evaluated the effect of an additional linear lesion at the roof of the left atrium on the long-term outcome.

Methods

A total of 300 patients (155 men, 145 women; mean age 72 years (SD ± 18 years)) with symptomatic persistent atrial fibrillation underwent a circumferential pulmonary vein ablation procedure in combination with an additional linear lesion at the roof of the left atrium (group A). After discharge, patients were scheduled for repeated visits at the arrhythmia clinic at 1, 3, 6, 12, 24, 36, 48, 60, 72, 84, 96, 102, 108, 120, 132, 138 and 144 months after the ablation procedure.

The long-term follow-up data was compared to 300 patients who underwent circumferential pulmonary vein ablation without an additional linear lesion at the roof of the left atrium (group B).

Results

The ablation procedure could be performed as planned in all patients.

Sixfty-six out of 300 patients (22.0 %) in group A and 69 out of 300 patients (23.0 %) in group B experienced an arrhythmia recurrence within the first 3 months after ablation requiring an electrical cardioversion. At 144-month follow-up, analysis of a 168-hour ECG recording revealed no evidence for an arrhythmia recurrence in 171/300 patients (57.0 %) in group A and in 141/300 patients (47.0 %) in group B. In 87/300 patients (29.0 %) in group A and 78/300 patients (26.0 %) in group B, only short episodes of paroxysmal atrial fibrillation were documented. In 42 patients (14.0 %) in group A, a recurrence of persistent atrial fibrillation (> 48 hours) was revealed by the long-term recordings (group B: 81 patients (27.0 %)). The lower arrhythmia recurrence rate in group A was partially due to a lower incidence of atypical atrial flutter after catheter ablation. The rate of repeat ablation procedures was significantly lower in group A than in group B. There were no major complications.

Conclusions

Catheter ablation of persistent atrial fibrillation comprising a circumferential pulmonary vein ablation and an additional linear lesion at the roof of the left atrium provides more favourable results than circumferential pulmonary vein ablation alone. The effect is more pronounced during long-term than during short-term follow-up.
Results of atypical flutter ablation in the era of high density electroanatomical mapping (the RAFAELA study)
Authors: Lozano-Granero C , Moreno J , Sanchez-Perez I , Matia-Frances R , Hernandez-Madrid A , Zamorano J L , Franco E
Published: November 2023

Introduction

Atypical flutter (AFL) ablation is a technically challenging procedure with limited long-term efficacy according to prior studies and not exempt from risks.

Purpose

The aim of this study was to describe the efficacy, in terms of acute and long-term rhythm management, and safety of AFL ablation guided by high-density electroanatomical mapping in a population of contemporary patients. We aimed also to compare results between different patient populations.

Methods

From june 2015 to November 2021, all consecutive AFL ablation procedures guided by high-density electroanatomical mapping were included in the study. Patients were classified in 4 groups according to history of atrial catheter ablation, cardiac surgery, congenital heart disease or none of the above (considered as primary disease). Activation and voltage mapping were used to define AFL circuits and substrate. After AFL characterization, radiofrequency lesions were performed to operator’s discretion until AFL termination. Programmed atrial stimulation was repeated to test AFL inducibility, and any sustained induced atrial arrhythmia was ablated. Procedural success was defined as termination of every induced AFL and no-inducibility. A 3-month blanking period was considered. Follow-up included visits with ECG and/or 24h Holter-ECG at 3, 6, 12, 24 months, and from there on according to physician’s discretion.

Results

190 AFL procedures in 160 patients were included. Patient and procedural characteristics of the global cohort as well as different patient populations (27% primary, 37.9% post-ablation, 15.3% post-surgery, 20% congenital heart disease (CHD)) can be found in figure 1 (table).

Survival free from atrial arrhythmias in pre-specified groups is shown in figure 2 (left). Overall, a 2-year ∼50% recurrence rate was observed, with a tendency to better outcome in patients with congenital heart disease (∼70%), over the rest of the groups, which behaved similarly (p=0.281). Progression to permanent atrial arrhythmia was lower in this subgroup (2.7% vs 23.5%, p=0.028), as shown in figure 2 (right), probably related to higher rhythm control efforts and stricter follow-ups.

CONCLUSIONS

In the era of high-density electroanatomical mapping, acute procedural success is achievable in the majority of patients, but recurrence rate remains high, with an approximate 50% 2-year recurrence rate except for congenital heart disease patients, which tend to show better survival free from atrial arrhythmias.Figure 1Figure 2
Risk of stiff left atrial syndrome following pulse-field-based ablation of atrial fibrillation in patients with pulmonary hypertension at baseline
Authors: Mohanty S , Della Rocca D G , Chierchia G B , Dello Russo A , Casella M , Gianni C A R O L A , Macdonald B , Mayedo A , La Fazia V M , Torlapati P G , Bassiouny M , Gallinghouse G J , Horton R , De Asmundis C , Natale A N D R E A
Published: November 2023

Introduction

Studies have reported development of stiff LA syndrome, defined as pulmonary hypertension (PH) secondary to reduced LA compliance, in some patients following AF ablation.

Purpose

We compared the risk of worsening of baseline PH in non-paroxysmal AF (persistent and long-standing persistent AF) patients undergoing repeat procedures, either pulse-field ablation (PFA) or standard radiofrequency ablation (RFA).

Methods

This multicenter study included 28 non-paroxysmal AF patients with PH, undergoing PFA-based ablation procedure after >1 failed radiofrequency ablations (RFA). A cohort of 28 AF patients with PH that were scheduled for repeat RF ablation were identified. Propensity scores were computed using multivariate logistic model. Twenty-eight patients from the RFA cohort were selected by 1:1 propensity score matching with the PFA group. Right heart catheterization was performed pre- and post-procedure to assess the Pulmonary artery pressure (PAP).

PH was defined as resting mean PAP of ≥20 mmHg. The follow-up PAP and change from baseline were compared between PFA and RFA groups, after controlling for baseline PAP in an ANCOVA model.

Results

Baseline characteristics of PFA (age 62.21 ± 9.3 yrs, male 19 (67.9%), LAD 3.7 ± 0.66 cm) and propensity-matched RF groups (age 62.39 ± 9.3 yrs, male 18 (64.3%), LAD 3.7 ± 0.74 cm) were comparable. The mean pulmonary artery pressure (PAP) assessments at baseline, follow-up and change from baseline are presented in table below. The groups had comparable baseline PAP (p= 0.157). At follow-up, RF group reported 19.81 mm Hg increase in PAP (within-group p <0.001). In PFA group, follow-up PAP showed a decreasing trend (-1.67 mm Hg, within-group p= 0.114). Compared to PFA, the change was significantly higher in RFA (p <0.0001) after controlling for baseline PAP).

Conclusion

In this propensity-matched population, pulse-field ablation was demonstrated to be a safer option in terms of post-ablation worsening of PAP, compared to the RF ablation in AF patients with pulmonary hypertension at baseline.
Impact of active esophageal cooling on catheter ablation procedure times across five healthcare systems
Authors: Joseph C , Cooper J , Zagrodzky J , Kulstad E , Bailey S , Sherman J , Nazari J , Athill C , Daniels J , Mcdonald S , Ruppert A , Willms D , Kawasaki R , Turer R , Metzl M
Published: November 2023

Background

Increased efficiency in procedure times may improve electrophysiology lab throughput and enhance patient care. The choice of esophageal protection method during pulmonary vein isolation (PVI) can affect procedural efficiency, with recent data suggesting that active esophageal cooling is associated with shorter procedure times when compared with luminal esophageal temperature (LET) monitoring.

Objective

To compare PVI procedure times before and after the adoption of active esophageal cooling in a large multicenter analysis.

Methods

Procedural data were obtained from 5 hospital systems before and after they adopted active esophageal cooling. Patient age, gender, and total procedure time were recorded and compared between groups before and after adoption of esophageal cooling.

Results

A total of 2,280 patient procedures completed by 16 different physiologists were reviewed from a total of 6 hospitals. The hospitals included academic medical centers, community hospitals, and integrated healthcare delivery systems. Prior to adopting active esophageal cooling, patients were treated with LET monitoring using either single or multi-sensor temperature probes. For the actively cooled patients the mean age was 66.7 ± 10.9 years and 33.5% were female. For the LET monitored patients the mean age was 64.2 ± 10.7 years and 34.5% were female. A total of 928 patients were treated with LET monitoring, with a mean procedure time of 173 ± 73 minutes. A total of 1352 patients were treated with active esophageal cooling, with a mean procedure time of 113 ± 51 minutes, representing a decrease of 60 minutes, or 34.7% of procedure time, compared with active esophageal cooling (P<.001).

Conclusions

Active esophageal cooling during PVI was associated with up to a 34.7% reduction in procedure duration when compared to LET monitoring in this large multicenter analysis.
Long-term success rates of a stable, low pressure cryo balloon for the treatment of paroxysmal atrial fibrillation - results of the prospective, international, multicenter POLAR-ICE study
Authors: Luik A , Anic A , Asmundis C , Champ-Rigot L , Iacopino S , Martin C A , Sommer P , Tilz R R , Yap S C , Albrecht E M , Raybuck J , Richards E , Cielen N , Defaye P
Published: November 2023

Background/Introduction

Pulmonary vein isolation (PVI) using a cryo balloon is well-established for the treatment of paroxysmal atrial fibrillation (PAF). Compared to other available technologies, the usage of a stable, low pressure cryo balloon (POLARx, Boston Scientific) has demonstrated lower nadir temperatures and longer thawing times. However, long term efficacy and safety still needs to be proven.

Purpose

The aim of the POLAR-ICE Study was to evaluate long-term efficacy and safety outcome of cryo balloon ablation in patients with paroxysmal atrial fibrillation.

Methods

POLAR ICE, a prospective, non-randomized, international, multicenter study, enrolled 399 patients across 19 centers, between Aug 2020 and May 2021. Patients with paroxysmal atrial fibrillation undergoing de novo PVI were included into the study. During the index procedure, procedural characteristics, such as time to isolation (TTI), cryoablations per pulmonary vein, balloon nadir temperature, and occlusion grade were recorded. Procedural success was defined as successful isolation of each vein proven by entrance block. Follow up visits were at 3, 6, and 12 months. Recurrence is defined as any documented (ECG/Holter) episode of atrial fibrillation / atrial tachycardia longer than 30sec. after a blanking period of 3 months.

Results

399 patients (mean age 61 years, 36% female) were included into the study. After 12 months, freedom from any arrhythmia was 83.5% and freedom from atrial fibrillation 88.1% (Figure 1). Procedure/ablation related Serious adverse events occurred in 8.7% of patients, and included access complications (2.6%), cardiac tamponade (0.5%), air embolism (0.3%), AV block (0.3%), effusion (0.3%) phrenic nerve palsy (0.3%), stroke (0.3%), transient ischemic attack (0.3%). Redo procedures have been conducted in 19 patients. In 14/19 pts reconnection of at least one PV could be identified (RSPV n=8, RIPV n=12, LSPV n=9, LIPV n=11). Freedom from any arrhythmia was associated with lower nadir temperature (p=0.008) and longer time to thaw (p=0.05) during the index procedure.

Conclusions

In this prospective, non-randomized, international, multicenter study, isolation of the pulmonary veins using a stable, low pressure cryo balloon was highly effective and safe in patients treated for paroxysmal atrial fibrillation. Lower nadir temperatures and a longer thawing time were predictors of clinical success.
Pulsed field ablation and ventricular capture: assessing the need for R-wave gated therapy
Authors: Tranter J , Piorkowski C , Pipenhagen C , Mittal L , Boudlali H , Hughes B , Thao R , Fish J
Published: November 2023

Background

Pulsed field ablation (PFA) is a therapy that disrupts cellular homeostasis by applying high intensity and short duration electrical pulses to cardiac tissue, ultimately resulting in cell death. Such stimuli have the potential to initiate ventricular arrhythmias if the therapy is not synchronized with the beginning of ventricular systole (R-wave gating). For the treatment of cardiac arrhythmias, it is important that the candidate therapy locations in the left atrium (e.g., pulmonary veins) are a sufficient distance away from ventricular tissue to avoid ventricular capture. Objective data exploring the need for R wave gating in the context of PFA therapy for pulmonary vein isolation is currently lacking.

Purpose

To study the effect of electrode distance of the 12-electrode loop catheter from the epicardium on likelihood of ventricular capture.

Methods

A sternotomy was performed on swine to expose the heart. An incision was then made in the pericardial sac and the edges were lifted and sutured to the surrounding chest cavity to create a cradle. The function of the cradle was to hold a ∼37C saline solution (tuned to match the electrical conductivity of blood) while PFA treatments were performed. Two left ventricular sites (apex and lateral aspect) were selected for treatment, taking care to avoid proximity to the coronary artery. For each PFA therapy trial, the catheter loop was positioned 10mm above the surface of the epicardium and then advanced in 1mm increments until capture was achieved; spacers were used to assure fixed spacing during cardiac activity. For each trial, the maximum distance between the catheter and the epicardium at which the IRE therapy captured the ventricle was recorded. Additionally, CT scans (N=20 human patients) were analyzed to understand distances of interest to ventricular tissue.

Results

N=12 trials were conducted at each target in each animal (N=48 total ablations). For all trials, the minimum capture distance was found to be 6-8mm (4/48 at 6mm, 28/48 at 7mm and 16/48 at 8mm), with a mean capture distance of 7.25±0.60mm. The mean capture distances for the left ventricular apex and lateral aspect were 7.29±0.55mm and 7.21±0.66mm, respectively (p=0.636).

For the CT scan analysis, the minimum distance from pulmonary vein ostia to left ventricular tissue ("nominal case") were 10.6mm and 12.8mm for the left superior and inferior veins, respectively. Considering the use ("worst case") where the catheter is placed just distal to the ostia, the distances to ventricular tissue were 1.6mm and 5.8mm, respectively; 4/20 patients had a vein less than 10mm from ventricular myocardium.

Conclusions

This study was successful in establishing the distance of ventricular capture via PFA therapy (6-8mm for the considered therapy). Given the described use and CT analysis, there is potential risk in triggering ventricular arrhythmia via PFA therapy unless R-wave triggering is implemented.
High-power short-duration ablation of the atrioventricular node
Authors: Alsaiqali M , Ahmed R , Alsaiqali G , Budzikowski A , Jallad A
Published: November 2023

Introduction

There are limited studies that compare different radiofrequency ablation catheters in atrioventricular node (AVN) ablation. Our study compared the effectiveness of several radiofrequency ablation catheters in AVN ablation.

Methods

We identified patients who underwent AVN ablation at our institution. Data related to patients and procedures were collected through retrospective chart review. The radiofrequency catheters compared were plain non-irrigated, externally irrigated (EI), and contact force sensing in two different settings: low-power long duration (LPLD) and high-power short duration (HPSD). We compared the different catheters in terms of success rate using logistic regression and lesion time using linear regression.

Results

We identified 66 patients who underwent AVN ablation, out of which 31 were female (47%). The patients were elderly, with a mean age of 73.27 years. The indications were resistant atrial fibrillation in 74%, atrial flutter in 18%, and other atrial tachycardias in 8% of patients. Types of catheters used were plain non-irrigated in 48%, EI in 2%, LPLD in 16%, and HPSD in 34% of patients. All ablation procedures were successful with no immediate post-procedure complications. Regarding lesion time, HPSD was significantly shorter compared to plain catheters by 403.42s[-631.67, -175.17] as shown in table 1.

Conclusions

While plain catheter, LPLD, and HPSD were equally safe and effective, HPSD catheter had significantly shorter lesion time and thus procedure time.
Analysis of thermal effects from pulsed field ablation
Authors: Mercado Montoya M , Gomez Bustamante T , Kulstad E , Mickelsen S , Gonzalez Suarez A
Published: November 2023

Background

Pulsed field ablation (PFA) has been described as non-thermal, but abundant data exist in oncology applications [1-3], and growing data are emerging in cardiology [4], highlighting that thermal effects are in fact present with PFA. The particular parameters (such as voltage, pulse gap, pulse number) that most influence the development of thermal energy during PFA are less clear.

Purpose

We sought to evaluate the thermal effects arising from pulsed field ablation of myocardial and esophageal tissue over a range of typical peak voltage operating conditions.

Methods

Using a three-dimensional computer model of the left atrium and esophagus, we quantified the thermal effects from PFA applications over a range of peak voltage operating conditions (1 kV, 1.5 kV, and 2 kV). Bipolar electroporation was simulated using one electrode as the anode and the other as a grounded cathode. Far-field and symmetry boundaries were set as electrically insulating. A monophasic waveform with a pulse duration of 100 µs and pause between pulses of 1 s was applied for a total of 50 pulses in a single train. Myocardial thickness was 1.5 mm, esophageal thickness was 2 mm, and the pericardial fat layer was varied between 0.3 and 0.75 mm.

Results

Minimal temperature rise in the esophagus was seen with 1 kV pulses (corresponding to 13.4 J input). With 1.5 kV and 2 kV peak voltages (corresponding to 32.3 J and 66.2 J), temperature elevations reaching 46.3 °C and > 62 °C were seen, respectively. These elevations occurred after only a single pulse train of 50 pulses, implying that further elevations in temperature would be seen with subsequent applications.

Conclusions

Thermal effects from PFA depend on total energy deposited, of which peak voltage is an important component. Current commercially available systems appear to have the potential to induce collateral thermal injury, particularly with a thin pericardial fat layer, and with repeated applications of pulsed field energy.
New mapping for determination of left atrial posterior wall isolation for non-paroxysmal atrial fibrillation
Authors: Suzuki A , Amemiya M , Usui M , Yamauchi Y
Published: November 2023

Background

Recent studies have reported that the efficacy of posterior wall isolation(PWI) created by cryoballoon for non-paroxysmal atrial fibrillation. However, there are no clear criteria for determining whether or not to perform PWI, and it is left to the discretion of the operator. Then we evaluated the necessity of additional PWI by measuring non-passively activated ratios(%NP), the ratio of the form of rotors and multiple wavelets, using ExTRa mapping and verified its usefulness.

Methods and Results

44 patients with non-paroxysmal atrial fibrillation who underwent cryoballoon ablation(CBA) were divided into two groups according to whether using ExTRa mapping(ExTRa group; 21 patients) or not(no-ExTRa group; 23 patients), and the long-term results were compared. In ExTRa group, ExTRa mapping was performed before PVI, after PVI, and after roof block(LA-RB) creation using cryoballoon. After creating LA-RB, if more than 50% of %NP remained in the left atrium, PWI was performed by creating a bottom block(LA-BB) using cryoballoon. After a median follow-up period of 12months(2 to 34 months), arrhythmia-free survival rate was higher in the ExTRa group than in the no-ExTRa group(95.2% vs 69.6%, p<0.05%).

Conclusion

Evaluation of %NP using ExTRa mapping is extremely useful in determining the additional PWI for non-paroxysmal atrial fibrillation.Voltage mapping & ExTRa mapping
Same day discharge after interventional electrophysiology procedures, first German experience
Authors: Popescu S S , Heeger C H , Vogler J , Eitel C , Feher M , Kirstein B , Phan H L , Marburg M , Breithaupt C , Delgado Lopez M L , Kuck K H , Tilz R R
Published: November 2023

Background and purpose

In most European countries, the current postprocedural gold standard following electrophysiological (EP) interventions implies the overnight monitoring of the patients in the hospital. Due to limited healthcare capacities and an increasing safety profile of ablation procedures, the mandatory overnight monitoring is under debate.

Same day discharge protocol (SDD) ablation might be a safe and efficient alternative. We present the first German experience on SDD for EP interventions.

Methods

Patients receiving interventional EP procedures with a maximum of two VAs were discharged on the day of procedure, after the hemostasis and ambulation were proven. The VA hemostasis was achieved either by using a vascular closure system (VCS) or by a figure-of-eight suture followed by compressive bandage application. All patients were scheduled for a medical visit the day after procedure for groin examination and suture removal.

Results

A total of 12 patients (25% females, median age 64 (57.3, 66.8) years, median BMI 30.5 (22.3, 33.7) Kg/m2) undergoing EP procedures followed the SDD protocol in our center.

All patients had an atrial fibrillation (AF) diagnosis, 66.7% of them paroxysmal. Five (45.5%) patients had a CHA2DS2VASc score of 1. A total of 4 (33.3%) patients presented arterial hypertension, 3 (25%) diabetes mellitus, 1 a history of stroke, 1 of myocardial infarction and 1 had chronic kidney disease and kidney transplantation. Eleven (91.7%) patients were under oral anticoagulation. The most common procedure was AF ablation, in 10 (83.3%) patients, while 1 (8.3%) patient underwent cavotricuspid isthmus (CTI) ablation and 1 (8.3%) a left atrial appendage closure procedure. In 10 (72.7%) AF ablations the energy source was cryoenergy, in 1 laserenergy and in 1 electroporation. The CTI ablation was performed by means of radiofrequency.

A VCS was used in 7 (58.3%) patients. Six of these patients received 2 VCSs, while the patient with PFA based ablation had a single vascular access, thus only one VCS. The procedure was reported successful in all cases, and no intraprocedural complication occurred.

During the next day visit, a groin hematoma has reported in 2 (16.7%) patients, no one requiring further therapeutical measures or hospitalization. All the other patients had no puncture related complications. The median FU time was 46.5 (26, 90.3) days. During FU only one patient had an unplanned ambulatory visit due to flecainide intolerance. Readmission during FU was reported in only 2 patients, none of them procedure related.

Conclusions

In selected patients undergoing EP procedures SDD seems to be safe and feasible. This approach increases healthcare capabilities, patients' comfort and reduces the cost of medical care.