bluuebunny/crossref_metadata_2025 huggingface dataset:
Body mass index may alter cardiovascular outcomes in patients with newly-diagnosed atrial fibrillation and previous stroke: an interaction analysis using longitudinal data from the GLORIA-AF registry
Authors: Lam S H M , Romiti G F , Olshansky B , Chao T F , Huisman M V , Lip G Y H
Published: October 2024

Background

Patients with new onset atrial fibrillation (AF) and previous stroke (PS) are at higher risk of cardiovascular (CV) outcomes. An obesity paradox, where overweight or obese patients have better outcomes, has been seen. Whether body mass index (BMI) modify the risks of cardiovascular (CV) events and mortality in AF patients with PS remains uncertain.

Purpose

To ascertain whether BMI of AF patients with PS events alters risks of CV outcomes.

Methods

A cohort from phase III of the prospective GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) was included. Risks of Major Adverse Cardiovascular Events (MACE), CV death, and all-cause mortality were analysed using COX proportional hazard regression with interaction terms added between PS and the BMI characteristics.

Results

Data from 17482 patients [median age: 71.0 (IQR: 64.0–78.0) years; 45.3% female] with newly-diagnosed AF were analysed and included in risk models. At baseline, 1840 (10.5%) patients with AF had PS in which 1694 (9.7%) and 170 (0.97%) patients had one (1 PS) and ≥2 (2 PS) respectively. After a median follow-up of 3.0 (IQR: 2.9–3.1) years, 1111 MACE, 562 CV deaths, and 1266 all-cause deaths were recorded.

In a multivariate COX regression model, interaction between BMI and PS was significant in predicting risk of CV death (Pint =0.019). BMI was also associated with increased risk of CV death among AF patients with ≥1 PS. The interaction between PS and BMI was borderline significant in predicting MACE (Pint=0.063) and all-cause death (Pint=0.057). Figure 1 showed the different risks associated with different BMI statuses.

Conclusion

The risks of adverse CV outcomes were higher in AF patients with higher BMI and previous stroke. An obesity paradox was not evident in AF patients with previous stroke.Figure 1
Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: implications of insulin treatment: a report from the GLORIA-AF Registry Phase III
Authors: Liu Y , Chen Y , Lam S H M , Huang B , Chao T F , Olshansky B , Huisman M , Lip G Y H
Published: October 2024

Background

Atrial Fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations has not been fully elucidated, especially in relation to insulin use.

Purpose

To analyze the associations between DM and the risk of clinical adverse events in patients with AF, and second, explore the impact of insulin treatment in these patients.

Methods

We studied patients with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-years follow-up. Clinical events included all-cause death, major bleeding, myocardial infarction (MI), stroke, thromboembolism (TE), and major adverse cardiovascular events (MACE). MACE was defined as a composite of stroke, MI and major bleeding. Kaplan-Meier curves were used to estimate the cumulative incidence of clinical events. Multivariable cox regression models with subgroups were used to estimate the association between DM and the risk of mortality and clinical events.

Results

A total of 15,861 AF patients were included (mean age 70.00 ± 10,21 years old; 55% male, 20% Asia), of which 3,666 had DM (mean age 70.04 ± 9.54 years old; 59% male, 21% Asia). Kaplan-Meier curves showed that AF patients with DM had higher cumulative hazard of all outcomes, including all-cause death (OR: 1.56, 95%CI: 1.38-1.77), CVD (OR: 1.72, 95%CI: 1.44-2.06), major bleeding (OR: 1.4, 95%CI: 1.17-1.67), stroke (OR: 1.29, 95%CI: 1.04-1.61), TE (OR: 1.26, 95%CI:1.02-1.56), MI (OR: 1.88, 95%CI: 1.48-2.39) and MACE (OR: 1.61, 95%CI: 1.41-1.84). After adjustment by prior disease and drugs, the outcomes of stroke (OR: 1.19, 95%CI: 0.95-1.49) and TE (OR: 1.22, 95%CI: 0.98-1.52) showed not significant. Subgroup analysis found that increased risks of stroke were found in female (OR: 1.43, 95%CI: 1.03-1.98, Pinteraction = 0.062) and non-Asian patients (OR: 1.39, 95%CI: 1.06-1.82, Pinteraction = 0.175) with DM. For all cause death, subgroup results were similar with overall patients. In addition, insulin use increased the risk of all cause death (OR: 1.82, 95%CI: 1.45-2.29), CVD (OR: 1.70, 95%CI: 1.22-2.37), major bleeding (OR: 1.54, 95%CI: 1.08-2.18), MI (OR: 1.72, 95%CI: 1.12-2.64), MACE (OR: 1.65, 95%CI: 1.28-2.11) in patients with AF and DM. Multivariable model showed similar result.

Conclusions

DM was independently associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF. Insulin use was associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF and DM.Figure 1Figure 2
Temporal and age-related trends in risk factors for development of atrial fibrillation in peripartum patients
Authors: Yu E , Ali B A , Mehta N K M , Karim S K
Published: October 2024

Background

Incidence of atrial fibrillation (AF) in pregnancy has steadily increased over the past two decades and may be related to changes in rates of AF risk factors.

Objective

To characterize trends in the prevalence of AF risk factors among patients with peripartum AF.

Methods

TrinetX, a large national healthcare database, was used to identify patients with peripartum AF from 2017-2022. Inclusion criteria were female patients aged >18 years old who received a diagnosis of AF within one month prior to and one year after a diagnosis of pregnancy. Annual prevalence of pre-existing AF risk factors, including diabetes, chronic kidney disease (CKD), obesity, and hypertension, were obtained, normalized to the annual number of peripartum AF cases, and followed. In a second analysis, student’s t-test and standardized mean difference were used to compare the rates of AF risk factors between patients with peripartum AF and pregnant patients with no history of AF within the same time frame. Comparisons were performed across age ranges.

Results

From 2017-2022, there were 6,465 patients with peripartum AF and 2,852,348 pregnant patients with no AF. There was an increase in the proportion of peripartum AF patients with pre-existing obesity (16.7% to 18.5%) and hypertension (28.9% to 33.7%). In comparing pregnant patients with no AF history with peripartum AF patients, the standardized mean difference for rates of all risk factors increased with age group. The peripartum AF group had significantly higher rates of all risk factors across all age groups (p < 0.0001 for all groups).

Conclusion

Rates of pre-existing obesity and hypertension increased among patients with peripartum AF, which could be a factor in increasing rates of peripartum AF. Differences in rates of AF risk factors between peripartum AF patients and pregnant patients with no AF were more pronounced at older age groups.
Polygenic risk score for prediction of atrial fibrillation according to presence of the hypertrophic cardiomyopathy
Authors: Lee Y , Yang P , Jang E , Kim D , Yu H T , Kim T H , Uhm J S , Sung J H , Pak H N , Lee M H , Kim J B , Joung B
Published: October 2024

Background

The significance of genetic predisposition in predicting atrial fibrillation (AF) is well recognized, yet its role in hypertrophic cardiomyopathy (HCM) patients remains less clear.

Objective

In this study, we aimed to elucidate the impact of genetic risk on the development of AF in both HCM and non-HCM patients.

Methods

This retrospective analysis examined 1,180 HCM patients (mean age 61.1±7.1, 63.0% male) and 476,238 non-HCM patients (mean age 57.0±8.1, 45.3% male) from the UK Biobank. Participants were stratified based on their validated polygenic risk score (PRS) for AF: the bottom 10% constituted the low genetic risk group, the top 10% comprised the high genetic risk group, and the remainder fell into the intermediate genetic risk group. We assessed the incidence of AF and major cardiovascular events and analyzed predictors, including genetic risk.

Results

Among HCM patients, no significant differences in baseline characteristics were observed based on genetic risk, except for the rate of CIED implantation (P=0.036). Conversely, among non-HCM patients, variations in age, gender, and comorbidities were noted according to genetic risk. The HCM patients were categorized into three groups based on risk, with respective AF incidence rates of 2.4, 3.6, and 5.4 events per 100 person-years, respectively. In non-HCM patients, the incidence of AF per 100 person-years was 0.2, 0.5, and 1.0, respectively. Genetic risk emerged as a significant predictor of AF in both HCM and non-HCM patients, although with a higher hazard ratio observed in non-HCM patient (HR, 2.51; 95% CI, 1.59–3.98 vs. HR, 4.77; 95% CI, 4.47–5.09) (P=0.003 for interaction). In non-HCM patients, predictors of AF included age, male sex, body mass index, smoking history, and a history of hypertension, diabetes, heart failure, stroke, and myocardial infarction, in addition to PRS. However, in HCM patients, only age, diabetes, and a history of stroke were identified as independent predictors of AF. Moreover, high genetic risk was significantly associated with the risk of major adverse cardiovascular events.

Conclusions

In conclusion, our study indicates associations between genetic predisposition and AF occurrence in both HCM and non-HCM patients.
Proteinuria and the risk of incident atrial fibrillation according to diabetes stage in patients with diabetes: a nationwide population-based cohort study
Authors: Yeo M , Lee S R , Choi E K , Choi J M , Lee K Y , Kim B S , Ahn H J , Han K D , Lip G Y H
Published: October 2024

Background

Proteinuria and diabetes mellitus (DM) are established cardiovascular risk factors, both independently associated with an increased risk of atrial fibrillation (AF). Despite previous findings correlating proteinuria amount with incident AF, regardless of DM diagnosis, the nuanced association at different stages of DM warrants further investigation.

Purpose

This study aimed to delve into and compare the relationship between proteinuria amount and the risk of incident AF in patients across various stages of DM.

Methods

A cohort of 3,866,428 individuals without prior AF and type 1 DM, who underwent the 2009 health checkup provided by the National Health Insurance Service in Korea, were categorized into five DM stages: normal, prediabetes, new-onset DM, early DM (diagnosed < 5 years), and late DM (diagnosed ≥ 5 years). Proteinuria was graded using the urine dipstick test, ranging from negative to 3+ or more. AF incidence was tracked until December 31, 2020.

Results

The cohort, with an average age of 47.0 ± 13.9 years and 45.4% females, demonstrated escalating annual AF incidence rates from 1.90 to 6.45 per 1000 person-years across DM stages (p<0.001) (Figure). Similarly, the rates increased from 2.28 to 7.28 per 1000 person-years by proteinuria levels (p<0.001) (Figure). Adjusted Cox regression models revealed a heightened risk of incident AF associated with higher proteinuria amounts in all DM stages (adjusted hazard ratios for urine dipstick 3+ or more: 1.57, 1.76, 1.44, 2.32, and 2.23, respectively). Notably, the association between proteinuria and incident AF was more pronounced in individuals with early and late DM compared to those with prediabetes and new-onset DM (Figure).

Conclusions

At each DM stage, from prediabetes to late DM, a higher level of proteinuria corresponds to an increased risk of AF development. Furthermore, a stronger association was observed in patients with longer DM duration compared to those with prediabetes or new-onset DM. These findings underscore the significance of monitoring proteinuria levels across DM stages to assess AF risk comprehensively.
Post-operative atrial fibrillation during cardiac rehabilitation: incidence and long-term prognostic value
Authors: Cacciola G , Lazzeroni D , Ziveri V , Rastelli S , Geroldi S , Camaiora U , Brambilla L , Brambilla V , Donelli D , Magnani G , Moderato L , Ardissino D , Niccoli G , Nicolini F , Bini M
Published: October 2024

Background

Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery and is associated with longer in-hospital stay and increased in-hospital death and stroke, but its long-term prognostic value, during cardiac rehabilitation (CR), remains not well understood.

Purpose

The study aimed to assess the incidence and long-term prognostic values of different types of POAF in a cohort of consecutive patients who undergo CR after cardiac surgery.

Methods

A consecutive registry of patients admitted to our CR after cardiac surgery represents the present study. POAF was defined as any episode of atrial fibrillation occurring in the post-operative period from post-intensive care unit to hospital discharge after CR; moreover, POAF types were classified as Paroxysmal POAF (early and late) and persistent (early and late). Long-term hard end-points were: cardiovascular (CV) mortality and major adverse cardiovascular and cerebrovascular events (MACCEs defined as a composite of cardiovascular death, heart failure hospitalization, non-fatal myocardial infarction, and stroke).

Results

A total of 2.020 patients were included, mean age was 67 years and male gender was prevalent (71%). CR post-coronary artery bypass graft (CABG) was the indication of CR in 53% of patients, cardiac valve surgery in 35%, while 11% underwent CR after CABG plus valve surgery. All patients were followed for a mean of 50 months. POAF was found in 392 patients (19.4%) divided into 36% paroxysmal POAF and 64% persistent POAF, while 7.7% had permanent atrial fibrillation (figure 1A).

Overall POAF was associated with higher rates of CV death (SR 5.0% vs POAF 7.2% vs pAF 16.5%; p<0.001) and MACCEs (SR 12.4% vs POAF 19.6% vs pAF 25.2%; p<0.001 – figure 1B).

By analyzing separately paroxysmal, persistent, early, and late POAF, interestingly only late POAF (both persistent or paroxysmal) was associated with a higher long-term CV risk, in particular, both late persistent and late paroxysmal were associated with a higher risk of MACCEs (late persistent: OR 1.65, p=0.004 / late paroxysmal: OR 1.98, p=0.002 – figure 1C), mainly driven by a higher rate of heart failure hospitalization. Interestingly late paroxysmal POAF showed the worst outcomes among all classified POAF (figure 1D).

Conclusions

POAF after cardiac surgery is associated with long-term adverse outcomes, but not all POAF have the same prognostic value. Late, rather than early, POAF (whether paroxysmal or persistent) is associated with a poor long-term prognosis after cardiac rehabilitation.Figure 1
Prognostic implication of right ventricular - pulmonary arterial coupling in patients with non-valvular atrial fibrillation
Authors: Kim D , Ryu S , Jang J , Shin S
Published: October 2024

Background

The clinical importance of right ventricular (RV) - pulmonary arterial (PA) coupling has been reported in various cardiac diseases such as right heart failure, pulmonary hypertension, and valvular dysfunction. However, there is limited data on patients with non-valvular atrial fibrillation (AF). We aim to investigate whether RV-PA uncoupling affects the clinical outcome in patients with non-valvular AF.

Methods

A total of 807 consecutive patients with non-valvular AF who underwent echocardiography (mean age 70 ± 12 years, 39% female) were included. We excluded patients with significant (at least moderate degree) valvular diseases, left ventricular ejection fraction (LVEF) <50%, cardiac implantable electronic devices, previous cardiac surgery, and poor echocardiographic image for RV analysis. RV-PA coupling was assessed by the ratio of RV global longitudinal strain (GLS) to PA systolic pressure (PASP), and decreased RV-PA coupling was defined as less than 0.52 %/mmHg based on on the receiver operating characteristic analysis. The primary outcome was the composite of all-cause death and hospitalization for heart failure.

Results

Over a mean of 4.7 ± 3.5 years of follow-up, 178 (22%) patients had experienced primary outcomes. Among them, 107 (13%) patients were hospitalized for HF and 90 (11%) patients died. Patients with decreased RV-PA coupling were older (73 ± 11 vs. 68 ± 12 years, p<0.001), had a higher prevalence of females (51 vs. 33%, p<0.001) and diabetes (33 vs. 23%, p=0.003), lower left ventricular ejection fraction (60 ± 5 vs. 61 ± 5%, p=0.011), higher E/e’ (14 ± 5 vs. 11 ± 4, p<0.001), larger left atrial volume index (78 ± 37 vs. 62 ± 22 ml/m2, p<0.001) and larger RV end-systolic area (11 ± 4 vs. 10 ± 3 cm2/m2, p=0.001) compared to those with preserved RV-PA coupling. In multivariate Cox regression analysis, decreased RV-PA coupling was associated with worse clinical outcomes even after adjusting for age, diabetes, E/e’, and RV end-systolic area (Hazard ratio [HR] 1.50, 95% Confidence interval [CI] 1.09 – 2.07, p=0.014) (Figure 1).

Conclusions

In patients with non-valvular AF, RV-PA coupling was associated with clinical outcome, suggesting that it may provide additional information for predicting future cardiovascular risk in this population.
Atrial fibrillation detection on implantable loop recorders in embolic stroke of undetermined source
Authors: Chattopadhyay R , Chousou P A , Matthews G , Clark A , Vassiliou V , Pugh P J
Published: October 2024

Introduction

Embolic stroke of undetermined source (ESUS) represents 17% of all ischaemic strokes, and has a 5% annual stroke recurrence risk. Recent large randomised control trials failed to demonstrate a benefit of empirical anticoagulation for all ESUS patients, with sub-analyses supporting the need for a tailored approach to those patients at greatest risk of atrial fibrillation (AF) development. Understanding how the increased incidence of ILR-detected AF in the ESUS cohort, compares with ILR-detected AF in other cohorts is an essential step in understanding the significance of this finding.

Purpose

To compare the incidence of ILR-detected AF following ESUS against patients undergoing ILR implantation for non-stroke indications for example syncope and palpitations.

Methods

We retrospectively studied all patients without known AF who were referred to our institution for ILR implantation following ESUS, syncope or palpitations from 2009 to 2019. The primary endpoint was any detection of AF or atrial flutter (AFL) by ILR. Kaplan-Meier and multivariable Cox-regression analyses were utilised to account for time-to-event.

Results

A total of 750 patients were included and followed up for a mean of 731 days (SD 443). An ILR was implanted following ESUS in 323 patients and for another reason in 427 patients (figure 1). The incidence of AF was significantly higher among patients with ESUS compared to the non-ESUS group; 48.6% versus 13.8% (for any duration of AF) and 32.2% versus 12.4% (for AF lasting > 30 seconds) both p <0.001. Kaplan-Meier analysis (figure 2), showed significantly higher incidence of AF for ESUS for any duration of AF. This was driven predominantly by AF duration <6 minutes and between 5.5 hours and 24 hours. Importantly, in a multivariable Cox regression analysis, ESUS independently conferred an almost 5-fold increase in the hazard for any duration of AF (Hazard Ratio 4.948, 95% confidence interval 3.587 – 6.825, p<0.001).

Conclusion

The incidence of AF is significantly higher amongst ESUS versus non-ESUS patients monitored constantly by an ILR. A high number of ESUS survivors have short duration AF episodes. Further work is needed to determine the optimal treatment strategy of these AF episodes in ESUS considering AF duration and overall burden.
Improved risk prediction in patients with atrial fibrillation and clinical intermediate-risk CHA2DS2VASc-score utilizing high sensitive troponin T
Authors: Salbach C , Yildirim M , Milles B R , Hund H , Biener M , Mueller-Hennessen M , Frey N , Katus H A , Giannitsis E
Published: October 2024

Background

Guidelines of the European Society of Cardiology recommend risk assessment to identify appropriate candidates for anticoagulation in patients with atrial fibrillation (AF). However, scores such as the CHA2DS2VASc-score show only a modest performance for prediction of adverse events.

Methods

This retrospective single-center all-comer sub-study from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB) enrolled 9,995 consecutive patients with non-valvular AF, presenting to the emergency department (ED) from June 2009 until March 2020. We tested the performance of the CHA2DS2VASc-score with and without high sensitive cardiac troponin T (hs-cTnT) for prediction of a adverse events such as stroke or major bleedings. Per CHA2DS2VASc, stroke risk was classified as low (0 point in men, ≤1 point in females), intermediate, or high (≥2 points in men and ≥3 points in females).

Results

Performance of the CHA2DS2VASc-score for the prediction of the composite endpoint consisting of stroke and major bleeding was poor (AUC 0.600, 95%CI: 0.590-0.610) but improved after addition of hs-cTnT as a variable across all risk categories (AUC 0.618 95%CI: 0.608-0.628, ∆AUC 0.0182 95%CI: 0.0124-0.0240, p<0.0001), and particularly in patients at intermediate-risk (∆AUC 0.160 95%CI: 0.0653-0.254, p=0.0009). The absence of detectable hs-cTnT (< LoD) identified a cohort without incident events within patients with intermediate per CHA2DS2VASc.

Conclusion

Combination of hs-cTnT and clinical-based risk stratification in AF patients presenting to an ED with intermediate CHA2DS2VASc-score is simple and effective. Measurement of hs-cTnT improves prediction of stroke risk in patients with intermediate CHA2DS2VASc-score and may help guide decision for or against anticoagulation.
Atrial function after cardioversion in patients with persistent atrial fibrillation
Authors: Noda K , Sunamura S , Onodera K , Tanita A , Ogata T , Takii T , Namiuchi S
Published: October 2024

Background

After cardioversion for persistent atrial fibrillation (AF), restitution of normal left atrial (LA) function is said to need several days to recover. However, in previous studies, the evaluation of LA function was only used transesophageal or transthoracic echocardiography. During catheter ablation (CA) for AF, pulmonary venous (PV) blood flow can be measured accurately using an intracardiac echocardiogram (ICE). The atrial systolic PV regurgitation (PVa) wave measured by ICE is a good indicator of LA contractility because it reflects the active contraction of the LA.

Purpose

This study aims to investigate the LA function in the hyperacute phase and the factors which affect after cardioversion.

Methods

40 AF patients (18 paroxysmal AF, 22 persistent AF) who underwent CA were enrolled. PVa wave was measured twice before RFCA and after the procedure using intracardiac ultrasound. Voltage map of the LV was obtained using the CARTO system at the end of the session, and the percentage of low voltage area which was determined area as less than 0.1mV in the mapped LA surface area (LVA%) was calculated.

Results

Preoperative PVa was 1.61 ± 0.09 m/sec in the paroxysmal AF group (PaAF), and no PVa was observed in the persistent AF group (PeAF). Postoperative PVa were comparable between PaAF (0.18±0.06 m/sec) and PeAF (0.18±0.07 m/sec). Then, the PeAF were divided into 2 groups based on LVA% in the anterior area, posterior area, and total LA area (cutoff 1,5 and 10%, respectively). In the anterior lower LVA% group, PVa were significantly increased (0.20 ± 0.07 m/sec) after defibrillation compared with the anterior higher LVA% group (0.14 ± 0.06 m/sec; P=0.02), whilst no difference was observed when it was divided in the posterior wall or overall.

Conclusion

Even in PeAF, LA function improves to the same degree as in the PaAF immediately after cardioversion, and the posterior wall LVA, including posterior wall isolation, may not affect LA function.
Sulcardine, an investigational multichannel blocker for atrial fibrillation with uniquely intense JTp inhibition to enhance safety
Authors: Mason J , Elliott G , Romano S , Gillings M , Riebman J
Published: October 2024

Background

Sulcardine is a multi-ion channel blocker for treating atrial ﬁbrillation (AF) with similar inhibitory potency on peak/late sodium, L-type calcium, and rapidly activating delayed-rectiﬁer potassium (IKr) currents. The therapeutic effect of inhibiting IKr includes QT prolongation (accompanied by a proportional J to T peak [JTp] interval prolongation), which, when excessive, may cause malignant arrhythmias. As previously reported, sulcardine strongly mitigates the JTp increase that may contribute to excessive QT prolongation by inhibiting late sodium and L-type calcium currents, an intrinsic mechanism to protect from excessive IKr block.

Purpose

We explored the JTp mechanism, pharmacokinetics (PK), electrocardiogram (ECG) changes, safety, and drug-drug interaction (DDI) of a single sulcardine (as HBI-3000) intravenous (IV) infusion in healthy subjects.

Methods

An open-label Phase 1 study evaluated the PK interaction between sulcardine, dosed as a 350 mg 30-minute infusion of the sulfate salt HBI-3000, and a cytochrome P450 CYP2D6 enzyme inhibitor (paroxetine). Triplicate ECGs were extracted from continuous 12-lead Holter ECG recordings at baseline and 10 time points thereafter. Mean baseline-subtracted and heart rate-corrected QTcF (dQTcF), JTpc (dJTpc), and other ECG changes were calculated at each time point. Left ventricular ejection fraction (LVEF) was assessed at baseline, 30-, and 120-minutes post-infusion start by transthoracic echocardiography (TTE).

Results

39 subjects received HBI-3000, 33 in the paired PK population. Expected ECG parameter changes proportional to sulcardine plasma concentrations were observed in the HBI-3000-alone portion of the study, including modest QTcF prolongation (Fig 1, blue slope, conﬁdence band) and JTpc inhibition (Fig 1, red). The usual JTpc increase associated with IKr blockers, even those with mitigating channel block (such as the late sodium current), was not only reduced but actually reversed. We calculated the dQTcF change that would have been observed in the absence of JTpc reduction by sulcardine (Fig 1, green). Sulcardine reduced the QTcF increase that might have occurred by about 21 msec at the highest concentrations, and this mitigating effect was observed at all concentrations. No clinically significant safety ﬁndings or arrhythmias were observed. The most frequent TEAEs were nausea and headache (n=2 each [5.1%]). No LVEF changes were clinically significant. Sulcardine had minimal metabolic interactions.

Conclusion

Acute IV HBI-3000 administration resulted in no clinically significant safety findings, LVEF depression, or DDI with CYP2D6. Sulcardine facilitates QT prolongation, which has a therapeutic benefit in terminating AF, with simultaneous uncoupling and reversing of the JTpc interval increase, a potential mechanism for reducing proarrhythmic risk due to excessive QT prolongation.Figure 1.ECG Intervals vs Sulcardine Conc
Safety and effectiveness of pulsed field ablation for pulmonary vein isolation in atrial fibrillation patients: a single centre experience
Authors: Reis Santos R , Bello A R , Santos P G , Matos D , Rodrigues G , Carmo J , Sousa M , Costa F , Carmo P , Morgado F , Cavaco D , Haas A , Adragao P
Published: October 2024

Introduction

Atrial Fibrillation (AF) is the most frequent arrhythmia in the world with an exponentially increasing prevalence. Pulmonary veins (PV) are the primary triggering sites for AF and pulmonary veins isolation (PVI) is currently the standard therapy alongside pharmacological treatment and should be considered as first-line treatment. Pulsed-fieldablation (PFA) is a novel ablation modality that involves the application of electrical pulses causing cellular death, with preferential tissue specificity.

Aim

In this study, we evaluated the safety and efficacy of single-shot PFA in AF patients.

Methods

Single-center registry of consecutive patients undergoing PVI using the pentaspline PFA catheter (all with CARTO3D system v.7 and high-density mapping), between June 2022 and November 2023. Data on demographics, procedural characteristics, and electrocardiographic recurrence (assessed after a 3-month blanking period) were analyzed.

Results

152 consecutive patients were included (63 ± 10 years, 57% male), with a mean CHA2DS2-VASc score of 2±1 points, median LVEF of 60% (IQR 59-65%), and a median CT-scan derived left atrial volume index of 56 mL/m2(IQR 44-69 mL/m2). A total of 40% had non-paroxysmal AF and a redo procedure was performed in 17% of patients. The median procedure time was 78 min (IQR 58-111 min) and fluoroscopy time was 11.6 min (IQR 8.2-15.6 min). Additionally, posterior wall isolation (PWI) was performed in 63 patients (41%). There were no esophageal complications, phrenic nerve injuries, cerebrovascular events, or procedure-related deaths. Two patients (1.3%) experienced acute cardiac tamponade, immediately treated with pericardiocentesis. Other complications were primarily vascular, in 5% of cases (4 femoral hematomas, 3 femoral pseudoaneurysms, 1 arteriovenous fistula). Over 293 (IQR 170 - 394) days of follow-up, considering electrocardiographic recurrence, 12% of patients had AF recurrence (5 with paroxysmal AF and 10 with persistent AF). These patients were older (69 ± 7y vs. 62 ± 11y, p=0.016), were more likely to undergo a redo procedure (33 vs. 8%, p=0.004), and had a higher percentage of posterior wall isolation (21 vs. 8%, p=0.038).

Conclusions

PFA for PVI wall ablation is safe and effective, with 100% intraprocedural technical success, a low rate of complications, and a high percentage of patients free from AF in the short-term.
Early repeat catheter ablation in patients with early recurrent arrhythmia
Authors: Jiang T , He L , Wang Z X , Liu N , Ma C S
Published: October 2024

Background

Repeat catheter ablation reduces adverse cardiovascular endpoints in patients with recurrent atrial tachyarrhythmia after index ablation. However, when to proceed with re-ablation in patients with early recurrent arrhythmia is unknow.

Objective

In this study, we aim to access the effectiveness of early repeat ablation on cardiovascular outcomes in early recurrent atrial tachycardia patients.

Methods

A total of 502 post-ablation patients, who experienced early atrial tachyarrhythmia recurrence within 6 months outside the blank period post index ablation and had undergone a repeat ablation, were consecutively enrolled from China AF registry from January 2012 to December 2018. Early repeated ablation (ERA) was defined as patients underwent a subsequent catheter ablation procedure within early recurrent period, then late repeated ablation (LRA) referred to a redo procedure that performed after 6 months since the de novel ablation. Cox proportional hazard models were used to estimate the effect of early re-ablation on primary endpoint (a composite of cardiovascular death, stroke and cardiovascular rehospitalization) and secondary endpoint (each component of primary outcome and AF/AT recurrence).

Results

The median follow-up time was 26 months after the redo-AF/AT ablation. First primary composite outcome occurred in 39 of the patients received early re-ablation (24.38 per 100 person-years) and in 136 of the patients performed with late re-ablation (39.77 per 100 person-years) (HR = 0.55, 95% CI = 0.38-0.79; P0.001). Cardiovascular re-hospitalization (hazard ratio 0.52 95% confidence interval [0.36; 0.73]) and AF recurrence occurred less often (hazard ratio 0.76, 95% confidence interval [0.58; 0.98]) in the ERA group. No significant difference between the two groups was found in terms of cardiovascular death, stroke and major bleeding events.

Conclusion

Early initiation of redo-ablation conveys better clinical benefit in patients with early arrhythmia recurrence.
Risk factors for procedure-related complications in very elderly patients undergoing atrial fibrillation ablation: analysis from the Japan Ablation Registry
Authors: Inoue I , Nakai M , Yamane T , Kusano K , Takatsuki S , Satomi K , Iwanaga Y , Kanaoka K , Tonegawa K R , Sumita Y , Takegami M , Nakao M Y , Nogami A , Miyamoto Y , Shimizu W
Published: October 2024

Background

As atrial fibrillation (AF) ablation procedures become increasingly prevalent, understanding the risks of procedure-related complications is crucial, particularly in the very elderly population, defined in this context as patients aged 80 years and above. This study aimed to identify risk factors for complications in this demographic.

Methods

We conducted a prospective analysis of 170,017 AF ablation procedures from the Japan Ablation Registry, covering 482 facilities between 2017 and 2020. The analysis focused on patients aged 80 or older (very elderly group, n=14,389). Multivariate analysis was employed to identify risk factors for procedure-related complications in the very elderly, incorporating factors that showed a p-value of less than 0.1 in univariate analysis.

Results

Procedure-related complications were observed in 3.62% of the very elderly group. The multivariate analysis (Model 1) identified significant risk factors were the initial procedure (OR 1.30, 95% CI 1.01-1.67, p=0.041), type of AF (OR 1.34, 95% CI 1.03-1.74), and body weight (OR 0.99, 95% CI 0.98-1.00, p=0.082). For further analysis, the type of AF was categorized into paroxysmal AF (PAF), persistent AF (PeAF) and long-standing PeAF. We included these categories, along with the initial procedure and body weight, into further multivariate analysis (Model 2), which revealed that long-standing PeAF (OR 1.34, 95% CI 1.03-1.74, p=0.032), initial ablation (OR 1.30, 95% CI 1.01-1.67, p=0.042) and body weight (OR 0.99, 95% CI 0.98-0.99, p=0.001) were independently and significantly associated with complications.

Conclusion

This study identifies initial procedures, low body weight, and long-standing PeAF as significant risk factors for procedure-related complications in very elderly patients undergoing AF ablation. These findings highlight the importance of careful patient selection and tailored procedure planning for these subgroups in the very elderly population.
Risk and management of acute kidney injury resulting from hemoglobinuria following pulsed-field ablation in atrial fibrillation
Authors: Mohanty S , Della Rocca D G , Casella M , Compagnucci P , Torlapati P G , La Fazia V M , Gianni C , Chierchia G B , Gallinghouse G J , Burkhardt J D , Horton R , Al-Ahmad A , De Asmundis C , Dello Russo A , Natale A N D R E A
Published: October 2024

Background

High-voltage pulses can cause hemolysis leading to hemoglobinuria.

Purpose

We evaluated the prevalence of hemoglobinuria after pulsed-field ablation (PFA) and its impact on renal function in patients with atrial fibrillation (AF).

Methods

A consecutive series of 128 AF patients undergoing PFA were included in this analysis. The initial patients that did not receive post-ablation hydration were classified as group 1 (n=28) and the rest of the study population that received planned fluid infusion of ≥2 L after the procedure, were categorized as group 2 (n=100). Patients with estimated glomerular filtration rate (eGFR) <45 were excluded. All underwent extensive ablation beyond pulmonary vein isolation.

If urine tested positive for hemoglobin, blood samples were tested for Haptoglobin.

Results

Baseline characteristics of the study population are provided in Table 1.

Number of overall PFA applications were comparable between groups (group 1: 52.07±23.99 vs group 2: 59.83±22.78, p=0.149). Four patients in group 1 received 94.63±3.20 PFA applications. In group 2, 4 patients received >90 applications (94±2.82) and 2 patients received >150 (158.5±4.95) PFA applications.

Of the 28 in group 1, 21 (75%) developed hemoglobinuria during the 24-hour following catheter ablation. Mean post-ablation S-Cr was significantly higher than the baseline value in these 21 patients (1.46±0.28 vs 0.86±0.24, p <0.001). Of the 21, 4 (19%) patients that received a mean of 94.63±3.20 PFA applications had the S-Cr. >2.5 mg/dL (mean: 2.95±0.21). These 4 patients were also markedly oliguric (<400 ml/day) in the immediate post-ablation period.

Group 2 patients received significantly higher amount of fluid infusion following catheter ablation compared to group 1 (2092.53±198.94 vs 487.48±72.74 ml, p<0.001). None of the 100 patients from group 2 developed detectable hemoglobinuria or elevation of S-Cr including the 4 patients with >90 and 2 patients with >150 PFA applications.

Mean post-ablation Haptoglobin was 10.00± 8.40 (normal: 36–195 mg/dL). The accuracy of number of applications predicting Haptoglobin decline was excellent with the area-under the curve (AUC) 0.886 ± 0.068 with 95% CI of 0.754 – 1.000. (P-value = 0.002).

In multivariable analysis, both hydration (R-square 0.34, p <0.01) and number of PFA applications (R-square 0.40, p <0.038) were independent predictors of post-procedure acute kidney injury.

Conclusions

Based on our findings, number of PFA applications was an independent predictor of renal insult in patients receiving extensive ablation that could be prevented using planned fluid infusion immediately after the procedure.
Duration of sinus rhythm after direct current cardioversion does not predict recurrence of atrial fibrillation after subsequent catheter ablation: a multicentre study
Authors: Tang P T , Betts T R , Pedersen M E F , Rajappan K , Bashir Y , Wijesurendra R S , Ginks M R
Published: October 2024

Background

Catheter ablation (CA) for persistent atrial fibrillation (PsAF) is associated with high rates of AF recurrence. DC cardioversion (DCCV) is often performed before CA, with wide variation in duration of maintenance of sinus rhythm (SR) post-DCCV. Factors associated with short duration of SR after DCCV, such as raised body mass index, prior duration of AF, prolonged p wave duration on the 12-lead ECG, and indexed left atrial volume, are either associated with or indicative of atrial electrical and structural remodelling, suggesting that shorter duration of SR after DCCV reflects a more advanced substrate for AF, which could in turn also influence the likelihood of success after CA.

Objective

To determine if post-DCCV SR duration is associated with AF recurrence after subsequent CA.

Methods

We performed a multicentre retrospective study of patients undergoing first-time CA for PsAF between 2015-2018 with prior DCCV. SR duration after the last DCCV prior to CA was recorded. The primary outcome was the first recurrence of atrial arrhythmia post-CA (after a 90-day post-CA blanking period). We also performed a pre-specified sensitivity analysis for amiodarone use at DCCV, by performing repeat analysis after excluding all such patients across the three groups.

Results

A total of 331 patients were identified across five centres and categorised by post-DCCV SR duration: <7 days (group 1); 7-31 days (group 2); >31 days (group 3; Table 1). Over median post-CA follow-up of 591 days, 207 patients (62.5%) met the primary outcome. There was no significant between-group difference in the time to primary outcome (log rank p=0.82; Figure 1). There were significantly more blanking period arrhythmias in groups 1 and 2 than group 3 after post hoc Bonferroni correction (pairwise p=0.001, 0.002 respectively; Table 1). After exclusion of patients on amiodarone at time of DCCV, there remained no significant between-group difference in the time to primary outcome (log rank p=0.85).

Conclusion

Shorter duration of SR post-DCCV is associated with blanking period arrhythmia after CA, but crucially does not predict long-term AF recurrence. Early AF recurrence after DCCV should not influence decisions on CA suitability or be used to predict long-term CA success.
Weight change does not impact long-term outcomes following cryoballoon pulmonary vein isolation
Authors: Park L , Milstein N , Bhatt A , Preminger M , Sichrovsky T , Habibi M , Kochav S , Shaw R , Musat D , Mittal S
Published: October 2024

Background

Weight loss has been suggested to reduce frequency and burden of atrial fibrillation (AF) in overweight patients (pts). However, there are limited data on weight loss impact on outcomes in pts with AF who have undergone pulmonary vein isolation (PVI).

Purpose

To understand the impact of weight change on long-term outcomes, as assessed by freedom from recurrent AF in pts undergoing cryoballoon (CB) PVI.

Methods

We enrolled consecutive pts with AF who underwent CB PVI; all had implantable loop recorders (ILR) for long-term ECG monitoring. The cohort was divided into 4 groups based on weight change 1-year post ablation: (1) optimal weight loss (OWL) – weight decrease ≥ 10%; (2) minimal weight loss (MWL) - weight loss (WL) 3-9% weight decrease; (3) no weight change (NWC) - weight change < 3%, (4) weight gain (WG) ≥ 3% weight increase. We assessed for AF recurrence after excluding a 3-month post-ablation blanking period.

Results

Out of a total of 322 pts who underwent ablation, 241 (75%) pts (69 ± 10 years; 159 (66%) male; 133 (55%) PAF; CHA2DS2-VASc 2.7 ± 1.5; BMI 30 ± 5) had weight information available at ablation and last follow-up. All were off antiarrhythmics by 1 year. There were no differences in the 4 cohorts with respect to baseline characteristics. During the first year, about ¼ of pts were able to lose ≥ 3% of weight but only 8 pts (3%) were able to lose ≥ 10%. AF recurred in 153 (63%); they were older, more likely to have persistent AF (PeAF), and a higher CHA2DS2-VASc score. However, weight change did not impact outcome (Figure). In a multivariate Cox Regression hazards analysis, PAF vs. PeAF at ablation was the only factor associated with any recurrence at follow-up (Figure).

Conclusions

Post CB PVI only about ¼ of pts are able to lose weight. Weight changes in the first-year post ablation in obese pts did not alter outcomes with respect to likelihood of recurrent AF. These data should be taken into account when considering catheter ablation.
Role of 3D-electro-anatomical mapping on procedural characteristics and outcomes in pulsed-field ablation for atrial fibrillation
Authors: Badertscher P , Spreen D , Serban T , Isenegger C , Krisai P , Voellmin G , Osswald S , Knecht S , Sticherling C , Kuehne M
Published: October 2024

Introduction

While the utilization of dedicated 3D-electro-anatomical mapping (EAM) systems for catheter ablation of atrial fibrillation (AF) is crucial using radiofrequency, its potential benefits in pulsed-field ablation (PFA) remain uncertain. This is of particular interest, since some PFA ablation systems will soon be available with integrated 3D-EAM capabilities.

Objectives

To compare the procedural characteristics and outcomes of patients undergoing PFA for pulmonary vein isolation (PVI) with mapping and with no mapping.

Methods

We prospectively enrolled patients undergoing their first PVI at a tertary referral center. In patients undergoing PVI with mapping, a multipolar mapping catheter was used to create voltage maps during sinus rhythm pre- and post-ablation. In the non-mapping group PVI was confirmed by assessing entrance block via the PFA catheter. The first 30 cases with mapping were excluded to account for a potential learning curve.

Results

A total of 197 consecutive patients were included (age 65 [interquartile range (IQR) 58 – 72] years; indexed left atrial volume 40 [IQR 35 – 44] mL/m2). Among these, 127 patients (64%) underwent PVI with mapping and 70 patients (36%) with no mapping. The median procedure duration, left atrial dwell time and the fluoroscopic time for the mapping vs the non-mapping group were 55 [IQR 45 – 67] min vs. 28 [IQR 23 – 35] min (p < 0.001), 38 [IQR 30 – 49] min vs. 15 [IQR 11 – 21] min (p < 0.001), 11 [IQR 9 – 14] min vs. 8 [IQR 7 – 11] min (p < 0.001), respectively. In the mapping group in 9% (11/127 patients) at least 1 PV was incompletely isolated and required additional applications. Acute PVI success was 100%. There were two complications in the mapping group (one stroke, one coronary artery air embolism) and none were observed in the non-mapping group. The recurrence rate of atrial arrythmias during a median follow-up of 267 [IQR 164 – 419] days was 14% in the mapping group and 17% in the non-mapping group, p = 0.728.

Conclusion

In conclusion, the use of PFA with no mapping was associated with a significant decrease in procedural characteristics, while AF-recurrence was not significantly different. The routine use of mapping for PFA-PVI may not be needed.Figure 1
Organization of atrial flutter during pulse field ablation for atrial fibrillation
Authors: La Fazia V , Nicola Pierucci N P , Paolo Compagnucci P C , Domenico Giovanni Della Rocca D G D R , Carola Gianni C G , Mohanty Sangamitra M S , Preem Geeta Torlapati P G T , Rodney Horton R H , Gallinghouse Joseph G J , Amin Al-Ahmad A A A , Luigi Di Biase L D B , Carlo Lavalle C L , Michela Casella M C , Antonio Dello Russo A D R , Andrea Natale A N
Published: October 2024

Background

Pulse Field Ablation (PFA) has been acknowledged as an effective and safe tool for ablation of Atrial Fibrillation (AF). It is known that during AF ablation, the arrhythmia may organize into atrial flutter. The left atrial posterior wall is identified as a critical source of non-Pulmonary Vein (PV) triggers that facilitate maintenance of atrial fibrillation.

Objective

The purpose of this study is to investigate the phenomenon of atrial flutter organization from AF during the application of PFA.

Methods

This prospective multicentric study encompasses 117 consecutive patients with persistent AF across American and European institutions, undergoing first time catheter ablation. All receive isolation of the Pulmonary Veins (PV) plus Posterior Wall (PW) isolation. The PW isolation procedure targeted the standard area between the PVs and extended to the area demarcated by the line connecting the inferior borders of the inferior PV-encircling lesions to the coronary sinus defined lower part of PW (Fig. 1). The study documented the specific locations where AF organized into atrial flutter with a stable cycle length during PFA.

Results

Organization of AF to atrial flutter during PFA was observed in 72 (61.5%) patients. Analysis of the organization of flutter revealed that in 41 (56.9%) of these cases, flutter began while ablating the lower part of the PW. Moreover, 9 (12.5%) initiated at one of the PVs, and 22 (30.5%) during the ablation of the posterior wall. Notably, the flutter was described as perimitral flutter in 33 (45.8%), as typical flutter in 24 (33.3%), and as roof-dependent flutter in 15 (20.8%) of cases.

Conclusion

The findings underscore that during PFA for AF, there is a pronounced tendency for the arrhythmia to organize into atrial flutter, particularly during the ablation of the lower posterior wall. Notably ablation in the left atrium organized AF in typical atrial flutter at a considerable rate.Ablation on lower part of PW