bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of proNGF/NGF-NGFR-axis on the regulation of arterial remodelling
Authors: Takashima S , Usui S , Goten C , Inoue O , Takeda Y , Yamaguchi K , Hashimuko D , Sugita M , Sakai Y , Sakata K , Takamura M
Published: October 2024

Background

Peripheral blood mononuclear cells (MNCs) contribute to the pathogenesis of arteriosclerosis. Nerve growth factor receptor (NGFR) is present in peripheral blood and the ischemic coronary artery. NGFR transduces neurotrophin signals towards cell survival or apoptosis in different cell types dependent on coupling co-receptors. However, the role of NGFR-positive (NGFR+) MNCs in arterial remodelling is unknown.

Purpose

To investigate the functional mechanisms under which NGFR+ MNCs are involved in arterial remodelling.

Methods

Adult C57BL/6J male NGFR-wild-type (WT) or -bone marrow (BM)-specific (KO) mice were subjected to unilateral carotid artery ligation. The ligated and the opposite-sided, sham-operated arteries were assessed by immunohistology and gene expression analysis using a PCR on day 28. Also, human NGFR+ MNCs from a healthy volunteer were sorted using fluorescence-activated cell sorting and characterised using RNA sequencing. The cell apoptosis (AnnexinV+7AAD-) and chemotaxis in response to the ligands, NGF and its precursor proNGF, were assessed using flow cytometry and a Transwell migration.

Results

In WT mice, BM-derived NGFR+ cells accumulated in the neointima after ligation. The neointimal area was significantly greater in the BM-specific depletion of NGFR than in WT mice. NGFR+ cells in the neointima exhibited apoptosis (TUNEL+ and cleaved caspase-3+) accompanied by promoted F4/80+ macrophage and anti-inflammatory IL-10. By contrast, in the BM-specific NGFR-KO model, non-BM-derived SMCs increased in the neointima with augmented proliferation, and the accumulation of BM-derived cells and the expression of IL-10 were decreased. The expressions of proNGF/NGF and inflammatory cytokines, including IL-6, were not changed in a ligated artery, irrespective of NGFR+ depletion. Human NGFR+ MNCs expressed TrkB, TrkC, and sortilin co-receptors but not macrophage markers. Human NGFR+ MNCs, but not NGFR- MNCs, co-cultured with artery SMCs were susceptible to apoptosis in response to proNGF. Additionally, PDGF stimulated proNGF/NGF expression in SMCs, and proNGF/NGF did not affect the proliferation of SMCs in vitro. Furthermore, NGFR+ MNCs, but not NGFR- MNCs, increased migration toward NGF and did not show chemotaxis toward proNGF.

Conclusions

These data imply that local NGF might draw NGFR+ MNCs to the injured artery, in which proNGF induces NGFR+ MNCs apoptosis. Apoptotic NGFR+ cells promoted macrophage chemotaxis to resolve inflammation and decrease neointimal formation. Thus, we propose the proNGF/NGF-NGFR axis as potentially contributing to the suppression of arterial remodelling.
Clinical characteristic and zero-fluoroscopy ablation outcomes of tachyarrhythmias in pregnant: a single center study
Authors: Smagulova A , Ainabekova B , Albaev R , Abdrakhmanova Z H , Suleymen Z H , Abdrakhmanov A
Published: October 2024

Background

Although recommended avoid any intervention during gestation in cases of drug refractory of arrhythmias catheter ablation may be necessary in pregnant women.

Purpose

To present clinical characteristics and outcomes of zero-fluoroscopy catheter ablation during gestation.

Methods

This prospective, single center study included 84 cases of tachyarrhythmias during gestation. In 44 cases of drug refractory was performed catheter ablation without fluoroscopy (main group). We evaluated the further course of gestation and obstetric outcomes after ablation in comparison with pregnant with antiarrhythmic therapy of tachyarrhythmias (n=40, control group).

Results

Both groups were comparable by mean age of pregnant (28.2±4.2 vs. 27.3±3.9 years, p=0.093) and mean duration of gestation (24 ±3.4 vs. 23.8 ±3.2 weeks, p=0.123). New onset arrhythmia prevailed in both groups (64% vs. 55%, p=0,280). Supraventricular tachycardia was the most common arrhythmia during gestation (81,8% vs. 52,5%, p=0,005), which was followed by premature contraction (13,6% vs. 40%, p=0,007). Cases of ventricular tachycardia were rare (4,6% vs. 7,5%, p=0,665). Ablation was performed under the guidance of CARTO (45%) and Ensite Precision systems (55%) without using fluoroscopy in all cases. Acute procedural success of zero-fluoroscopy ablation was in 100% with mean procedural time 71±17 minutes without any complication. Outcomes: further course of gestation characterized by increased incidence of uterine contractile activity and placental abruption only in main group (4,54%, p=0.464 and 2.3%, p=642 respectively). There were no differences in the rate of other complication: uterine blood flow violation (15.9% vs 12.9%, p=0.234) and preeclampsia (4.55% vs 5%, p=0.237). Vaginal type of delivery was in the majority of cases in both groups (82% vs 83%, p=0.242). Neonatal outcomes characterized with normal range of fetal birth weight (median 3207,39±485,61 vs. 3312,3±234,1 grams, p=0.709) and 5 minute Apgar score (median 8,4±1,6 vs. 8,7±1,2, p=0.921). There was no incidence of maternal and fetal mortality. In 12 month, follow-up all there was no arrhythmia recurrence.

Conclusions

Zero-fluoroscopy ablation of tachyarrhythmias in pregnant is feasible and can be safety performed during gestation in cases of drug refractory with benign outcomes.
Macrophage heterogeneity in cardiometabolic disease
Authors: Zurke Y , Dib L , Park I , Cole J , Berthold D B , Udalova I A , Sansom S N , Monaco C
Published: October 2024

Metabolic diseases such as obesity and atherosclerosis are characterised by chronic inflammation that leads to the accumulation of immune cells in affected organs. Macrophages in the obese adipose tissue and the atherosclerotic plaque show transcriptional, phenotypic and functional heterogeneity. The accumulation of CD11c+ macrophages in atherosclerosis and obesity suggests the presence of conserved macrophage phenotypes in metabolic tissues.

We aimed to characterise shared and distinct features of monocytes and macrophages in the aorta and adipose tissue in the context of metabolic disease using single-cell techniques.

Single-cell RNA sequencing of the blood, aorta and visceral adipose tissue during a time course of metabolic disease progression (steady state, 12w western diet, 18w western diet) and data integration with murine aortic and adipose tissue community datasets revealed conserved and tissue specific features of metabolic disease. Resident macrophages in the aorta and adipose tissue displayed tissue specific transcriptional programs, highlighting that cell maintenance and function of tissue resident macrophages differ between metabolic tissues. Further, macrophages in the aorta and adipose tissue undergo disease associated compositional changes. For example, we uncovered distinct CD11c+ macrophage subsets that are conserved in the aorta and adipose tissue across multiple metabolic disease models and share core transcriptional signatures between both metabolic tissues. However, CD11c+ macrophage subsets showed tissue specific dynamics during metabolic disease progression. Overall, our analysis underscores that tissue niche affects macrophage composition as well as activation and transcriptional regulation patterns. Understanding similarities and differences between the two tissues will be important to inform identification of new therapeutic targets for cardiometabolic diseases.
Novel computational approach enables tailoring catheter ablation to a patient and evaluating the role of reverse remodelling in atrial fibrillation recurrence
Authors: Obada G , Ogbomo-Harmitt S , Deprez M , Aslanidi O
Published: October 2024

Background

Atrial Fibrillation (AF) is the most common cardiac arrhythmia affecting up to 2.5% of the population, decreasing the quality of life and increasing the chances of stroke five-fold. Radiofrequency Catheter Ablation (RFCA) is an emerging technique that warrants long-term curative treatment of AF. However, its success rate remains sub-optimal, with 50% of the arrhythmias recurring at 1-year follow-up. AF is a self-sustained condition that perpetuates by altering the atrial structure and cellular electrophysiological properties, the process referred to as remodelling. However, these changes can be reversible after successful AF treatment.

Aim

This study aims to create a novel, patient-tailored RFCA technique that targets re-entrant activity in the left atrium (LA), to test the technique in-silico, and to investigate the importance of reverse remodelling in AF recurrence after RFCA.

Methods

LA meshes with fibrosis were segmented from Late Gadolinium Enhanced Magnetic Resonance (LGE MR) images of AF patients (n = 13) and combined with the Courtemanche-Ramirez-Nattel (CRN) atrial electrophysiology model to create patient-specific 3D LA models. AF was initiated through the pacing at the end of effective refractory period (PEERP) protocol. The first ablation was automated to target the cores of re-entrant drivers. If this led to AF termination, recurrence was tested by pacing in the same 3D LA models with two variants of CRN electrophysiology: (i) AF-remodelled model, and (ii) healthy, i.e. reverse-remodelled model. If recurrence was present in either case, the second ‘redo’ ablation was performed using the same technique targeting the new re-entrant drivers. AF recurrence was then tested again (Figure).

Results

The first ablation terminated AF in all 13 patient-specific models. In the following PEERP test, AF recurrence rate was (i) 51.92% in the AF-remodelled cases (out of which, 37.04% of new drivers originating in the anterior wall, and 62.96% in the posterior wall). AF recurrence rate was only (ii) 5.77% in the reverse remodelled cases (all drivers originating in the posterior wall). The second ‘redo’ ablation was performed for all recurrent cases and terminated AF with 92.31% success rate. The second procedure also increased the freedom from AF after the PEERP test: (i) 37.5% recurrence for the remodelled cases (44.44% anterior, 55.56% posterior) and (ii) no recurrence in the reverse-remodelled cases.

Conclusion

This study shows the importance of reverse remodelling in the success of RFCA treatment for AF. In-silico ablation of patient-specific 3D LA models shows that AF recurrence drops to 5.77% and 0% after the first and second procedure, respectively, if the LA is reverse-remodelled. Our novel approach can be used to help improve clinical RFCA therapy.Computational pipeline for AF Treatment
Protamine administration after catheter ablation of atrial fibrillation using electroporation: a randomized controlled trial
Authors: Moravec O , Skala T , Vacha J , Klimes D , Seidler D , Stanke L , Klementova O , Taborsky M
Published: October 2024

Background

Safety of protamine administration after catheter ablation of atrial fibrillation (AF) using pulse-field system has not been previously described in a prospective randomized trial.

Methods

Consecutive patients with paroxysmal, persistent or long-standing persistent AF undergoing catheter ablation of AF using Farapulse system were randomly assigned in 1:1 ratio for protamine administration before sheaths removal. All vascular punctions were navigated using a direct ultrasound control. Right femoral vein was used for FaraDrive (16 F) sheath and left femoral vein for ICE (11 F) and decapolar diagnostic catheter (7 F). All sheaths were removed immediately at the end of procedure with subsequent local haemostasis with figure-of-eight suture. Primary endpoint was early and late access site complications. Secondary endpoints were significant bleeding, thromboembolic events and duration of hospital stay.

Results

428 consecutive patients were enlisted into the study (213 in protamine group; 215 in control group). Baseline and procedural characteristics were similar between both groups. ACT before venous sheath removal was higher in patients not receiving protamine (330.1 ± 38.6 vs. 189.3 ± 44.7 seconds, P < 0.001). There were no significant differences in both primary and secondary endpoints between both groups: groin hematoma (5 vs 5; p = NS); there were no thromboembolic complications in both groups and no significant differences of hospital stay duration.

Conclusion

Protamine administration after atrial fibrillation ablation using Farapulse system is not necessary when using ultrasound navigated vascular access and haemostasis with figure of eight suture.
Incidence of systolic heart failure and need for implantable cardiac defibrillators in patients with atrial fibrillation who had catheter ablation versus antiarrhythmic medical therapy
Authors: Ali B , Deluca M , Verma B , Yu E , Patel D , Patel R , Hassan A , Karim S
Published: October 2024

Background

The CASTLE-AF trial demonstrated that patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) who underwent catheter ablation (CA) showed improved patient outcomes. These outcomes included a reduction in all-cause mortality and heart failure hospitalizations along with an improvement in left ventricular ejection fraction, when compared to those receiving medical therapy alone. However, there is no data regarding development of novel HFrEF and the need for implantable cardiac defibrillator (ICD) in patients with AF who underwent CA vs. those on antiarrhythmic therapy (AAD).

Purpose

This study aims to assess if there is a difference in the development of HFrEF and the need for ICD intervention amongst AF patients who underwent CA vs. those on AAD. We hypothesize that patients with AF who underwent CA will have a decrease in the development of HFrEF and mitigation in the need for ICD intervention compared to AAD alone.

Methods

A large retrospective, multicentre database was utilized to identify patients aged 18-80 with AF from 2017-2023. Two cohorts were subsequently established based on treatment received: 1) CA vs. 2) AAD (amiodarone, flecainide, dronedarone, dofetilide, propafenone, sotalol). Patients with crossover between the groups were excluded. Student’s t-test was performed to compare baseline characteristics between cohorts. Relevant comorbidities, atrial fibrillation types, and cardiovascular medications were used for propensity matching. Kaplan Meier curves were calculated to compare outcomes at 5 years such as HFrEF development, ICD implantation, mortality, and hospitalizations.

Results

Patients that underwent CA (n=32,774) and AAD (n=345,882) were propensity matched yielding 32,670 patients per cohort. CA demonstrated a significantly decreased need for ICD intervention compared to AAD (1.69% vs. 3.28%; HR=0.559; 95% CI [0.503, 0.621], log rank p<0.0001). Secondary outcomes showed significant reduction in development of systolic heart failure (4.83% vs. 10.60%; HR=0.499; 95% CI [0.467, 0.533], log rank p<0.0001), overall hospitalizations (12.03% vs. 27.32%; HR=0.440; 95% CI [0.420, 0.461], log rank p<0.0001), and all-cause mortality (2.38% vs. 14.19%; HR=0.188; 95% CI [0.174, 0.203], log rank p<0.0001) with catheter ablation.

Conclusions

Patients that underwent CA had a significant reduction in development of systolic heart failure and mitigation in the need for ICD implantation when compared to those on AAD alone. Randomized clinical trials are needed to better understand this relationship and to further define which subpopulation of atrial fibrillation patients would derive the most benefit from CA.
Ablation strategy for patients with atrial fibrillation and heart failure - a Danish nationwide cohort study
Authors: Riis-Vestergaard L , Huth Ruwald M , Gislason G , Loch Hansen M
Published: October 2024

Introduction

Atrial fibrillation (AF) patients with heart failure (HF) face increased risks of AF recurrence and HF admission. Catheter ablation (CA) is a recognized treatment option. Due to observed atrial remodelling and fibrosis associated with ventricular remodelling in HF patients, it could be suggested that a more comprehensive ablation strategy should be applied for these patients.

Purpose

To examine the risk of AF recurrence and HF admission by ablation strategy for patients with AF and HF.

Method

This nationwide cohort study was conducted using real-life data from Danish healthcare registries. All patients above 18 years of age, with a diagnosis of AF and HF that underwent first-time CA from January 1st 2010 to December 31st 2018, were identified and included at the date of ablation. Exposure of interest was ablation strategy - pulmonary vein isolation (PVI) or additional ablation to PVI (PVI plus). PVI plus was defined as either roofline, mitral linear ablation, posterior wall isolation, complex fractionated atrial electrograms or ganglionated plexi ablation. Primary endpoint was HF admission and AF recurrence after a 3-months blanking period. AF recurrence was defined by a composite endpoint of first-reached endpoint of either use of antiarrhythmic drugs, AF admission, electrical cardioversions, or AF re-ablation. The relative rates of recurrent AF and HF admission by ablation strategy (PVI or PVI plus) were examined by Cox proportional models using PVI as reference. The analyses were adjusted for clinically important baseline characteristics including age, sex, AF type (paroxysmal or persistent), diagnosis-to-ablation time, procedural year, body mass index, size of left atrium, as well as co-morbidities such as ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease, hypertension, and diabetes.

Results

The study cohort consisted of 1,270 patients diagnosed with AF and HF undergoing first-time CA, of which 1,119 (88%) received PVI and 151 (12%) received PVI plus. 80% where males in both groups. Median age was 62 for the PVI group and 64 for the PVI plus group. Severely enlarged left atrium, ischemic heart disease and use of amiodarone were more prevalent in the PVI plus group compared to the PVI group (Table 1). The relative risk of recurrent AF showed a hazard ratio of 1.02 (95% CI: 0.77-1.37) for the PVI plus group compared to the PVI group, and for HF admission the hazard ratio was 0.95 (95% CI: 0.55-1.65) for the PVI plus group compared to the PVI group (Figure 1).

Conclusion

No significant differences in AF recurrence and HF admission were observed between PVI and PVI plus strategy in AF and HF patients in this observational study. With a diagnosis-to-ablation time exceeding 3 years, it could be argued that advanced atrial remodelling may diminish the impact of reverse atrial remodelling after catheter ablation, irrespective of the ablation strategy employed.Table 1Figure 1
Clinical findings from a large endo-epicardial atrial arrhythmia ablation registry
Authors: Manoharan K , Julia Calvo J J C , Mann I M , Amin R A , Mccready J M C , Silberbauer J S
Published: October 2024

Background

Despite advances, catheter ablation success rates for persistent AF remain at 50-60%. The approach for recurrent persistent AF, beyond pulmonary vein isolation, remains contentious. Surgical maze procedures have demonstrated superior outcomes compared to catheter ablation. Catheter-based linear lesions sets have failed to demonstrate efficacy, perhaps due to a lack of consistent transmurality with endocardial radiofrequency.

Objective

We report our safety and clinical data of an endo-epicardial approach using high-power radiofrequency ablation for atrial arrhythmias.

Methods

126 patients (80% male; mean age 65 years [43-81]) underwent redo ablation, between August 2020 and February 2024, for recurrent symptomatic atrial arrhythmias using an endo-epicardial approach. We used a standardised linear lesion set (posterior wall isolation and anterior mitral line) for recurrent persistent AF.

Results

Utilising an intentional coronary sinus exit and C02 insufflation technique, we achieved epicardial access in 121 anti-coagulated patients. 5 patients were found to have pericardial adhesions, prohibiting access. There were 2 LIMA punctures which were coiled, 2 cases of excess pericardial bleeding (not access related), that settled conservatively, and no surgery or death. 92% of patients received epicardial ablation. 86 anterior mitral lines (95% acute block, 79% with epi ablation), 88 roof lines (92% blocked, 50% with epi ablation) and 81 floor lines (98% blocked, 36% with epi ablation) were undertaken. 106 posterior wall isolations were performed (94% isolated, 51% epi ablation). 75 patients had a standardised lesion set and were included for recurrence analysis. 49 had persistent AF (71% male, mean age 65 years, mean LAVI 38 ml/m2, 26 PVI at baseline and 23 PV reconnections) and 26 longstanding persistent AF (92% male, median age 64 years, mean LAVI 37.1 mls/m2, 16 PVI at baseline and 10 PV reconnections). 82% with persistent AF (median follow up time 11 months) and 38% with longstanding persistent AF (median follow up time 10.1 months) maintained sinus rhythm. The submitted image demonstrates the freedom from persistent AF, for the cohort who are beyond the 3-month blanking period, as per classification of atrial arrhythmia.

Conclusion

In one the largest cohorts to date, we have shown that endo-epicardial atrial ablation is feasible and safe with epicardial ablation allowing improved transmurality and thus acute linear block. Clinical outcomes, using a posterior wall isolation and anterior mitral line, were favourable for persistent but not longstanding persistent AF.
HD grid versus circular mapping catheter for assessment of pulmonary vein (pv) reconnections
Authors: Manoharan K , Amin R A , Julia Calvo J J C , Mann I M , Mccready J M C , Silberbauer J S
Published: October 2024

Background

Traditionally, circular mapping catheters (CMC) have been considered superior to other designs for mapping pulmonary vein reconnections due to the circular shape of the PV ostium. The grid multipolar catheter produces higher definition maps potentially overcoming the disadvantage of being rectangular.

Purpose

We assessed the acute procedural results, comparing Grid versus CMC in the setting of PV re-isolation to understand if one was superior to the other.

Methods

In this multicentre randomised controlled trial, 169 patients (62% male; median age 66 years [22-83) underwent repeat ablation, between July 2021 and March 2023, for recurrent symptomatic atrial arrhythmias. We undertook two LA maps for patients, utilising the Grid and the CMC. Blinded maps were collected with both catheters, followed by randomisation to one map for analysis and ablation. The primary outcome was the radiofrequency time required to isolate the pulmonary veins. Secondary outcomes include LA mapping time and density for both catheters, ability to identify pulmonary vein sleeves and duration of the ablation procedure.

Results

126 patients had PV reconnections. 66 patients (64% male; median age 65 years [22-83]) in the Grid arm and 60 patients (68% male; median age 65.5 years [31-83]) in the CMC arm. There was one pericardial effusion and one TIA. There was no significant difference (p=0.202) found in the RF time required to achieve PV isolation in both Grid (mean RF time 200 ± 232 secs) vs CMC (mean RF time 169 ± 298 secs) arms. There was no significant difference (p=0.407) found between LA mapping time for the CMC (mean 1047 ± 454 seconds) and the Grid (Median 1080 ± 440 seconds). There was no significant difference (p=0.411) found in the total procedure time for the CMC (mean 122.7 minutes) and the HD grid (130 minutes). There were significantly more (p<0.001) PV mapping points identified with the grid (mean 354±213 points) than the CMC (mean 234±154 points) arm. There was no significant difference in PV sleeve reconnections found (p=0.106) between the grid (120 PV sleeve reconnections with a mean 1.4±0.71 reconnections) and the CMC (98 PV sleeve reconnections with a mean 1.52±0.72 reconnections). Both maps were analysed to assess reconnections on opposing catheter arms. The grid identified 20 PV sleeve reconnections not visible on the CMC, whilst 9 were visible on the CMC and not the grid.

Conclusion

There was no significant difference found in RF time, mapping time and overall procedure time. The Grid identified more reconnections not seen with the CMC and had an overall improved mapping density suggesting that this configuration could be superior for LA mapping.
Cardioneuroablation for the treatment of carotid sinus syndrome
Authors: Minguito Carazo C , Martinez Alday J D , Rodriguez Manero M , Martinez Sande J L , Garcia Seara J , Gonzalez Ferrero T , Elices Teja J , Fernandez Lopez X A , Garcia Rodeja F , Gonzalez Juanatey J R
Published: October 2024

Introduction

Carotid sinus syndrome (CSS), characterized by exaggerated vagal responses leading to asystolic pauses with carotid sinus massage (CSM), often necessitates pacemaker implantation. This study investigates cardioneuroablation (CNA) as an alternative management strategy for CSS.

Methods

Prospective study of consecutive patients referred for CNA. All patients underwent CSM, atropine test, 24-hour Holter monitoring and SF-36 quality of life questionary before the procedure and at 6 months. The objective of the study was to assess syncope free survival, grade of cardioinhibition with CSM and heart rate variation (HRV) and quality of life after the procedure.

Results

A total of 13 patients (84.6% male, mean age 63.8 ± 12.3 years) were included. After a median follow-up of 11.2 (10.6-16.3) months, none of the patients experienced syncope (0%) and none of the patients required pacemaker implantation. After the procedure all the patients had a negative CSM and only one patient (7.7%) had a positive CSM at 6 months (Figure 1). There was an improvement in the energy and health change items in the SF-36 quality of life questionary (Figure 2). There was a reduction in HR increase in the atropine test at 6 months (pre-CNA: 66% (52-84) vs. post-CNA 27.4% (21.9-90.9); p=0.027) and in most of the 24-hour Holter monitoring HRV parameters.

Conclusions

Cardioneuroablation emerges as a promising and effective alternative to pacemaker implantation in managing cardioinhibitory CSS. Further research is warranted to solidify these findings and explore the long-term effects of CNA in this scenario.Figure 1Figure 2
Comparative study of the effects of preferential left ventricular and biventricular pacing on echocardiographic and cardiorespiratory indices and clinical status of heart failure patients: preliminary
Authors: Xydis P , Dilaveris P , Chrysohoou C , Kordalis A , Laina A , Sideris S , Kalantzis C , Tsiachris D , Vouliotis A , Tsioufis K
Published: October 2024

Introduction

Nonresponse to cardiac resynchronization therapy (CRT) has been related with right ventricular dysfunction. Preferential left ventricular pacing (pLV-P) can achieve left ventricle resynchronization allowing for intrinsic activation of the right side, and benefit cardiac output while reducing atrial fibrillation occurrence. Moreover, the AdaptivCRT® algorithm also automatically adjusts interventricular (V-V) delay every minute.

Methods

We evaluated the effects of a pLVP algorithm on 100 systolic heart failure patients ( all Caucasians, 49% male; 67 +/- 8 years old; 51% ischemic cardiomyopathy; 44% diabetics; NYHA II-III) following randomization to standard biventricular pacing and pLVP, on echocardiographic and cardiopulmonary exercise test indices of functional status. Device programming was based on echocardiography-evaluated maximization of stroke volume and subsequent interventricular and atrioventricular delay adjustments delegated to the device. The follow-up consisted of 6 and 12-months visits; after the 1rst month of optimizing maximum CRT response.

Results

Significant comparative effects of pLV-P over optimized CRT were noted regarding right ventricle systolic velocity in TDI at 12-months from baseline (mean (SE); 4.5(0.8), p=0.035); decrease in end-diastolic volume of left ventricle (mean (SE); 11.33(7), p=0.035); decrease in right ventricle strain mean ((SE); 9.2(2.1), p=0.03). According to other echocardiographic indices, again taking into account baseline levels, patients in pLV-P group exhibited lower E/e value at 6-months (mean (SE); 8.390(4,3), p=0.04), and at 12 -months (mean (SE); 7.45(3.9), p=0.035); improved values in left atrium contractility strain at 12-months (mean (SE); 8.390(0.8), p=0.04); a borderline improvement in left ventricular ejection fraction (mean (SE); 8.7(433), p=0.05) at 12-months; and borderline improvement in left ventricular longitudinal strain at 6-months (mean (SE); 4.9(2.6), p=0.035), compared to optimized CRT. In CPET, taking into account baseline levels, patients in the pLVP group showed higher METs at 12-months (mean (SE); 1,16(0.8), p=0.03) compared to opt CRT group; higher predicted Ventilation rate (%) even from 6-months (mean (SE); 8.167(5,7), p=0.03) and higher predicted peak VO2 (%) at 6 months (mean (SE); 34,13(14), p=0.03) and borderline significance at 12 months (mean (SE); 4.88(3), p=0.08), compared to opt CRT.

Conclusions

In the preliminary findings of READAPT study, it seems that pLVP optimized by a standardized echocardiographic protocol in patients with preserved AV conduction and LBBB, can achieve improvement in parameters of right ventricular and left atrium structure and function, as well as in survival-predictive parameters of CPET compared to optimized CRT during the 12-months of follow-up.
Clinical validation of the 2021 European Society of Cardiology guidelines on pre-existing right bundle branch block patients undergoing transcatheter aortic valve replacement
Authors: Salis M , Badertscher P , Papa A , Knecht S , Nestelberger T , Kaiser C , Leibundgut G , Schaer B , Krisai P , Kuehne M , Sticherling C
Published: October 2024

Introduction

The management of patients with right bundle branch block (RBBB) undergoing transcatheter aortic valve replacement (TAVR) remains challenging. In these patients, the 2021 ESC guidelines recommend early pacemaker (PM) implantation in case of PR prolongation, QRS axis change or transient high-degree atrioventricular block (HAVB). However, evidence for the proposed criteria is scarce.

Purpose

Our aim was to evaluate the ESC recommendation for risk stratification of RBBB patients undergoing TAVR.

Methods

We retrospectively analyzed patients with pre-existing RBBB undergoing TAVR at our institution between 2011-2023. A surface 12-lead electrocardiogram (ECG) was available before and after procedure in all patients. The following, proposed ESC criteria were validated: ΔPR interval ≥ 20ms, QRS axis change or transient HAVB < 24 hours after TAVR.

Results

Of a total 1412 patients undergoing TAVR, 109 had pre-existing RBBB and were eligible for final analysis (mean age 83±5 years, 39% female). Of 109 RBBB patients, 36 (33%) developed persistent HAVB and received a permanent PM. Among the other 73 patients (67%), 17 patients (23%) suffered delayed HAVB during 30-days FU.

When applying the ESC Guidelines, PM placement would have been indicated in 52% (38/73) of patients with RBBB after TAVR: due to transient HAVB in 17 (23%), due to PR prolongation ≥ 20ms in 19 (26%) and due to QRS axis change in 20 patients (27%). The proposed ESC criteria identified 82% of patients (14/17) with delayed HAVB during 30-day FU, while missing 3 patients (18%, 2.8% of overall cohort, Figure).

This resulted in a sensitivity of 82% and a negative predictive value of 91%. Among the 17 patients with delayed HAVB, 12 patients (71%) displayed transient atrioventricular (AV) block within 24 hours after TAVR.

Conclusion

In this large cohort of RBBB patients undergoing TAVR with contemporary valves and techniques, the proposed ESC criteria of PR prolongation, QRS axis change or transient HAVB correctly identified 4/5 patients developing HAVB during 30-day FU. Prospective studies are warranted to confirm these findings.
Conduction system pacing and atrioventricular node ablation for atrial fibrillation - a systematic review and meta-analysis
Authors: Gin J , Ding Y C , Nalliah C , Farouque O , Lim H S , Kalman J , Wong G R
Published: October 2024

Background/Introduction

Biventricular pacing (BVP) has been shown to reduce the risk of heart failure following atrioventricular node ablation (AVNA) for the management of medically refractory atrial fibrillation (AF) when compared with conventional right ventricular pacing.[1] Conduction system pacing (CSP) is an emerging cardiac synchronization alternative to BVP[2], however, its evidence in AVNA for AF is limited.

Purpose

To evaluate the effect of CSP on left ventricular ejection fraction (LVEF), QRS duration (QRSd), pacing threshold and New York Heart Association (NYHA) class score following AVNA for AF.

Methods

We conducted a literature review of PUBMED, MEDLINE, EMBASE, Cochrane Library, and Web of Science for randomized clinical trials (RCTs) and observational studies evaluating CSP (His bundle pacing and left bundle branch pacing) post AVNA for AF. Out of 14 studies comprising 1112 patients, we conducted meta-analyses evaluating the impact of CSP on LVEF and QRS. Ten studies were pooled to assess outcomes pre- and post-implantation of CSP following AVNA. Three observational studies and one RCT were included in the meta-analysis comparing outcomes in CSP versus BVP post AVNA.

Results

CSP resulted in a significant QRSd reduction (-11.01 ms, 95% CI 5.07 - 16.95, p <0.01), improved LVEF (+10.28%, 95% CI 7.03 - 13.52; p <0.01) and improved NYHA score (-1.09; 95% CI -1.41 - -0.78; p <0.01) during follow-up of 6-36 months (Figure 1) from baseline (peri-implantation). There was no significant pacing threshold rise (0.11V; 95% CI -0.14 - 0.36; p= 0.39) observed during the same period. CSP was associated with statistically significant shorter QRSd (-49.81ms; 95% CI, -70.57 - -29.06; p <0.01) when compared to BVP. For LVEF, there was a statistically significant improvement of +8.96% (95% CI 2.55 - 15.37%; p <0.01) with CSP versus BVP. Limited data prohibited comparison of threshold and NYHA outcomes between CSP and BVP.

Conclusion

Conduction system pacing appears effective in improving baseline LVEF, QRSd and NYHA score in AVNA for AF, and may be a viable alternative to further optimising LVEF and QRSd in comparison to BVP. Further studies are required to evaluate the long-term impact and clinical outcomes of CSP in post AVNA patients.
Impact of Pirfenidone on arrhythmic and clinical outcomes in patients with idiopathic pulmonary fibrosis
Authors: Im S I
Published: October 2024

Background

Atrial fibrosis is an important substrate in atrial fibrillation (AF), particularly in the setting of structural heart disease. Previous study reported that pirfenidone, an antifibrotic agent, was beneficial at reducing myocardial fibrosis. The objective of the present study is to evaluate the effects of pirfenidone on arrhythmic and clinical outcomes in patients with idiopathic pulmonary fibrosis (IPF).

Methods

Our database of patients diagnosed with IPF from 2008 to 2023 was used to obtain echocardiography, electrocardiogram (ECG), and 24hr-holter monitoring data. Inclusion criteria were all IPF patients with/without Pirfenidone. And we compared arrhythmic events including atrial fibrillation, atrial premature complex, atrial tachycardia, ventricular arrhythmia and clinical outcomes according to use of Pirfenidone.

Results

Among 257 patients with IPF (74.0±8.9 years), 106 (42.1%) patients took Pirfenidone. Difference in the baseline characteristics was not observed. During the median 36-month follow-up, a lower incidence of arrhythmic events (P=0.001) and diastolic dysfunction (P=0.025) was observed in the Pirfenidone group. In univariate analysis, hypertension, coronary artery disease, higher body weight, longer PR interval, QRS duration, and less use of Pirfenidone were associated with arrhythmic events. In multivariate analysis, higher body weight and less Pirfenidone use were independent risk factors for arrhythmic events.

Conclusions

The use of Pirfenidone was associated with less arrhythmic events and lower diastolic dysfunction compared with no use of Pirfenidone in the long-term follow-up. And obesity was associated with higher incidence of arrhythmic events in IPF patients.
Semaglutide and atrial fibrillation: a systematic review and meta-analysis of randomized clinical trials
Authors: Costa G , Resende B , Cunha G , Guimaraes J , Fernandes D , Monteiro E , Lopes V , Sousa P , Antonio N , Elvas L , Goncalves L , Teixeira R
Published: October 2024

Introduction

Semaglutide is a glucagon-like peptide-1 receptor agonist that has been highly recommended for glycemic controland weight reduction. Obesity can also increase the risk of developing atrial fibrillation (AF).

Aims

To assess the association of semaglutide with cardiac arrhythmias, primarily AF.

Methods

We performed a systematic searched Pubmed, Embase and Cochrane database, between November and December 2023, to identify semaglutide’s randomized controlled trials (RCTs) with or without diabetic patients that reported new-onset cardiac arrythmias. A Mantel-Haenszel method and a random-effects model was used to calculate the odds ratio (OR) and 95% confidence interval (CI).

Results

16 RCTs were included, 6 with oral semaglutide and 11 with subcutaneous semaglutide. A total of 19892 patients were included, providing 137 new-onset AF. Our meta-analysis revealed a lower incidence of new-onset AF in semaglutide patients (pooled odds ratio [OR], 0.54; 95% confidence interval [CI] 0.39, 0.77, P < 0.01; I2 = 0%). Sub-analysis of oral and subcutaneous showed similar significant reduction (pooled OR 0.44; 95% CI [0.22, 0.87], P = 0.02, I2 = 0% and pooled OR 0.59; 95% CI [0.39, 0.88], P < 0.01, I2 = 0%, respectively). Significant reduction was also observed, regardless diabetic status. However, semaglutide revealed similar atrial flutter incidence (pooled OR 0.78; 95% CI [0.30, 2.05], P = 0.62, I2 = 0%), ventricular arrhythmias (pooled OR 1.68; 95% CI [0.77, 3.6], P = 0.19, I2 = 0%) and sudden cardiac death (pooled OR 1.68; 95% CI [0.77, 3.66], P = 0.19, I2 = 0%).

Conclusion

Our study suggests that in patients with or without diabetes, semaglutide reduces the risk of new-onset atrial fibrillation. This analysis provides an additionalcardiovascular benefit of this drug besides the major adverse cardiovascular events.
Integrating single-cell sequencing and genetic lineage tracing reveals endothelial plasticity during atrial remodeling
Authors: Zeng Z , Liu H , Wang X , Zheng Z
Published: October 2024

Background

Atrial fibrillation (AF), as the most burdensome cardiac arrhythmia, could lead to the significant mortality and morbidity. Atrial fibrosis is a well-recognized pathophysiological factor of the development and progression of AF, which also hampers its treatment. However, the underlying mechanisms of this intricate process remain largely unknown.

Purpose

This study sought to reveal the cellular composition of AF substrate and investigate the vital contributors to atrial structural remodeling.

Methods

Left atrial appendages from three patients with AF undergoing surgical ablation and three individuals with sinus rhythm undergoing heart transplantation were subjected to 10X single-cell RNA sequencing (scRNA-seq). Another five public scRNA-seq or snRNA-seq datasets of potentially remodeled right or left appendages were retrieved across three publications. The vital contributors of atrial structural remodeling and their characteristics were identified by intercellular communication analysis and trajectory inference. Transverse aortic constriction (TAC) was used to induce atrial remodeling in Cdh5-CreERT2;RFP mice, followed by scRNA-seq of endothelial cells (ECs). Human primary atrial ECs and fibroblasts were isolated for cell-cell interaction experiments. ECs-specific mouse models of Transforming growth factor beta 1 (TGFB1) (knockout and overexpression) were generated. Electrophysiological and histology analyses were performed to determine the consequences of ECs-derived TGFB1 gain and loss of function in the atrium.

Results

The comprehensive analysis of different scRNA-seq datasets revealed that ECs played an important regulatory role in the homeostasis of atrial substrate and displayed remarkable mesenchymal activation during atrial remodeling, which was further confirmed by TAC mice. Immunofluorescence staining and high-content screening suggested that the complete transition from ECs to mesenchymal cells slightly contributed to atrial remodeling. However, TGFB1 secreted from mesenchymal activated ECs significantly promoted activation, proliferation, and collagen secretion of fibroblasts. We discovered that overexpression of TGFB1 in ECs of mice significantly increased atrial fibrosis, and thus prolonging AF duration. Besides, knockout of TGFB1 in ECs of mice underwent TAC significantly attenuated the atrial fibrosis and decreased the rate of AF.

Conclusion

Our work demonstrates that mesenchymal ECs-derived Tgfb1 plays an important role in atrial remodeling by regulating the fibroblast function. EC-specific interventions were suggested to facilitate the development of novel strategies for mitigating AF substrate remodeling.
Mechanisms of atrial-fibrillation-induced ventricular dysfunction and recovery in the human left ventricular myocardium
Authors: Stengel L , Riedl D , Koertl T , Tirilomis P , Schramm R , Gummert J , Maier L , Streckfuss-Boemecke K , Pabel S , Sossalla S
Published: October 2024

Background

Atrial fibrillation (AF) frequently occurs alongside heart failure (HF). Clinical studies indicate improved left ventricular (LV) function following rhythm restoration but the underlying myocardial processes remain unclear.

Purpose

This study investigated effects of AF and its termination on human LV myocardium as well as potential molecular mechanisms involved in the AF-induced LV dysfunction.

Methods

Human LV tissue slices obtained from HF patients were long-term cultivated in-vitro. AF was simulated by tachy-arrhythmic culture pacing at 100 bpm with 30% irregularity for 7 days and contractile LV function was compared to slices undergoing sinus rhythm (SR)-simulation (60 bpm/0%). After 7 days, rhythm restoration was simulated by switching to SR-simulation.

To elucidate cellular mechanisms involved in AF-induced LV dysfunction, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were subjected to AF-simulation and examined via epifluorescence microscopy (FURA-2) and confocal microscopy (Fluo-4). Additionally, to investigate the impact of reactive oxygen species (ROS) on cardiomyocytes, iPSC-CM were subjected to treatment with the ROS-scavenger N-acetylcysteine (NAC).

Results

AF-simulation caused a progressive decline in systolic force of human LV myocardium (n=14 slices) with significantly reduced twitch amplitudes compared to SR-simulation (n=11). Within just 5 days of AF-termination, a significant recovery in LV function was observed, indicated by improved systolic contraction amplitudes. IPSC-CM measurements revealed a significant reduction in systolic Ca2+-transient amplitudes as well as an increased diastolic Ca2+ leak after AF-simulation (n=41) compared to SR-simulation (n=44). However, 5 days after SR-restoration, iPSC-CM exhibited no significant differences anymore, indicating a fast recovery of systolic Ca2+-cycling.

We further investigated the impact of ROS on LV function and could show that Ca2+-transient amplitude was preserved after AF-simulation in iPSC-CM when treated with NAC (n=35), suggesting an interplay of ROS with the Ca2+-homeostasis of cardiomyocytes.

Conclusions

This study demonstrates that AF impairs LV function in human HF myocardium. However, the involved changes in contractility and cardiomyocyte Ca2+ handling are reversible upon AF termination leading to improved LV function already within few days after AF cessation. Moreover, we provided an indication for an interplay of ROS with the Ca2+ homeostasis, endorsing an AF-induced LV-dysfunction, which merits further investigation.
Predictors of new-onset in-hospital atrial fibrillation in 122 089 patients admitted with COVID-19: an Australian statewide population study
Authors: Ne J Y A , Chow C , Chow V , Hyun K , Kritharides L , Brieger D , Ng A
Published: October 2024

Background

New-onset atrial fibrillation (AF) when encountered in COVID-19 patients may be associated with increased mortality and thromboembolic events. Few studies have investigated predictors of new-onset AF in the context of COVID-19 and no study has assessed the utility of CHA2DS2VASc score in predicting new-onset AF in COVID-19 patients.

Purpose

This study aims to identify independent predictors of new-onset in-hospital AF in patients admitted with COVID-19.

Methods

Patients admitted with COVID-19 (1-Jan-2020 to 30-Sept-2021) were identified from the Admitted-Patient-Data-Collection database in an Australian state, stratified by AF status (no-AF vs new-AF during index COVID-19 admission) and followed-up until 31-Mar-2022. Patients with prior-AF were excluded from analysis. New-AF was defined as new-onset AF during the hospital admission for COVID-19. Independent predictors of new-AF were identified using multivariable logistic regression. Receiver Operating Characteristic (ROC) derived Area Under Curve (AUC) score was performed to determine the predictive power of independent predictors of new-AF.

Results

The cohort comprised 122089 COVID-19 patients (median age 62.7 yrs; 48.5% males) of whom 5140 developed new-AF (4.2%). Compared to patients with no-AF, patients with new-AF had a higher prevalence of comorbidities and cardiac risk factors (hypertension, diabetes and smoking) as well as a higher CHA2DS2VASc score (p < 0.001) (Table 1). Independent predictors of new-AF included referral from Emergency Department (adjusted odds ratio [aOR] =1.63, 95% confidence interval [CI]=1.49-1.78, intensive-care-unit admission (aOR=3.46, 95%CI=3.22-3.71), current/ex-smoker (aOR=1.20, 95%CI=1.12-1.27), prior coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) (aOR=1.33, 95%CI=1.01-1.75), valvular heart disease (aOR=3.20, 95%CI=2.73-3.75), malignancy (aOR=1.15, 95%CI=1.02-1.29), chronic pulmonary disease (aOR=1.30, 95%CI=1.19-1.42) and higher CHA2DS2VASc score (per-1-score increase: aOR=1.62, 95%CI=1.59-1.65) (all P<0.05). CHA2DS2VASc score alone had an AUC score of 0.729 (95%CI=0.72-0.74) (Figure 1). Adding the above additional independent variables to CHA2DS2VASc score improved the predictive model to an overall AUC score of 0.773 (95%CI=0.77-0.78), p < 0.001.

Conclusions

This study identified patients at risk of developing new-AF in the setting of COVID-19 infection. Our multivariable logistic regression analysis that included CHA2DS2VASc score has a relatively good predictive value and if confirmed in other COVID-19 cohorts, may be used to identify patients in whom antiarrhythmic and more aggressive thromboprophylactic strategies can be considered.