Atrial Fibrillation Research Articles

Cardiac structure and function in patients with chronic obstructive pulmonary disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is common and strongly associated with cardiovascular disease, but the pathophysiology has not been fully elucidated. Purpose We aimed to investigate cardiac structure and function in patients with COPD compared to a matched general population. Methods In a prospective cohort study, 796 patients with COPD were included and matched 1:2 on age and sex with controls from a general population study. All participants underwent an examination program including echocardiography. Standardized linear regression coefficients were used to compare cardiac structure and function in patients with COPD vs. controls. Impaired left ventricular (LV) function was defined as a left ventricular ejection fraction (LVEF) <50%, or global longitudinal strain (GLS) <16% (numerical). Impaired right ventricular (RV) function was defined as tricuspid annular plane systolic excursion (TAPSE) <1.7 cm. Diastolic dysfunction was defined as having at least two of the following parameters: E/e’ >14, septal e’ velocity <7cm/s, or lateral e’ velocity <10 cm/s, left atrial volume index (LAVi) >34 mL/m2, or tricuspid regurgitation velocity (TRV) >2.8 m/s. Logistic regression was used to assess associations between having COPD and systolic and diastolic dysfunction. Results Mean age was 70.2 ± 8.3 years and 52% were females. COPD patients had a mean forced expiratory volume in 1 second (FEV1) of 49.4 ± 18.8% predicted. At baseline, 43% of the patients with COPD had hypertension and 10% had diabetes (DM). Additionally, 57% with COPD had cardiovascular disease at baseline, including 12% with ischemic heart disease (IHD), 15% with atrial fibrillation (AF), 6% with heart failure, and 5% with a previous ischemic stroke. Patients with COPD had impaired measures of cardiac structure and function including a lower GLS (COPD vs. controls: 16.3 vs. 19.2%), lower TAPSE (2.3 vs. 2.6 cm), larger LAVi (29.0 vs. 24.7 mL/m2), and higher TRV (2.7 vs. 2.3 m/s), p for all associations <0.001. (See figure). Patients with COPD had a significantly higher prevalence of impaired LV systolic function (OR for GLS <16%: 8.18, 95% CI(6.04; 11.1), p <0.001), impaired RV systolic function (OR for TAPSE <1.7 cm: 2.77, 95% CI(1.63; 4.69), p <0.001), and LV diastolic dysfunction (OR for diastolic dysfunction grade I or higher: 4.00, 95% CI(3.12; 5.13), p <0.001) after adjustment for age, sex, hypertension, smoking, DM, IHD, AF, and lower density lipoprotein. (See figure). Conclusion Patients with COPD had significantly impaired LV and RV systolic function as well as impaired diastolic function compared with individuals from the general population. These findings underscore the importance of recognizing and addressing cardiovascular comorbidities in COPD.

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

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

Long-term prognosis and predictors of death in chronic Chagas cardiomyopathy in women and men

Abstract Background Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of heart failure (HF) in Latin America and carries high morbidity and mortality. Previous studies showed conflicting results in epidemiological and clinical evidence of a gender-associated risk of death in patients with HF due to CCC. Purpose This study analysed the long-term prognosis and the main predictors of death in women and men with HF due to CCC. Methods From March 2009 to January 2023, we followed a cohort of outpatients with HF due to CCC. Specific serological tests diagnosed Chagas disease. Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) method to analyse time-to-event data and Cox proportional hazards methods to search for predictors of death. Results We studied 739 patients, with a mean age of 57.0 ± 12.1 years, 387 (52%) male. Women had a higher mean age (58.4 ± 11.7 vs. 55.8 ± 12.3 years; p=0.001), had a higher mean baseline left ventricular ejection fraction (LVEF) (44.3±14.5 % vs. 37.0±14.5%; p<0.001) and a smaller left ventricular diastolic diameter (LVDD) (56.8±8.9 vs. 62.5±9.4 mm; p<0.001). Over a median follow-up period of 10 years, 213 (56%) men and 169 (44%) women died (K-M: log-rank p=0.043; Figure). Men received more beta-blocker therapy (52.4% vs. 47.6%; p=0.040) and had a higher prevalence of chronic kidney disease (CKD) (p=0.003) and stroke (p=0.007). HFpEF was more prevalent in women and HFrEF in men (p<0.001). Device implantation and transplant were similar between women and men. Cox regression analysis for death adjusted for age, sex, myocardial infarction, diabetes, CKD, stroke, atrial fibrillation (AF), and LVEF showed LVEF (HR= 0.98;95%CL:0.97-0.98), age (HR=1.03;95%CL1.02-1.04) and CKD (HR= 1.32;95%CL:1.10-1.64) as the main predictors of death. In men, the main predictors were age (HR=1.02;95%CL:1.01-1.04), CKD (HR=1.409;95%CL:1.07-1.86), and LVEF (HR=0.98;95%CL:0.97-0.99), and in women AF (HR=1.41;95%CL:1.03-1.91), age (HR=1.03;95%CL:1.01-1.04), and LVEF (HR=0.97;95%CL:0.96 -0.98). Conclusion women had a better prognosis than men, but gender was not an independent predictor of death. Prevention of comorbidities, especially CKD in men and AF in women, and higher beta-blocker therapy can significantly reduce the death rate in women and men with HF from CCC.

Left atrial substrate modification for persistent atrial fibrillation and left atrial macro or microreentrant tachycardia using a single-shot pulsed field ablation system - a single centre case series

Abstract Background Pulsed field ablation (PFA) is a novel ablation technique for pulmonary vein isolation (PVI) in patients with paroxysmal and persistent atrial fibrillation. However, data for efficacy and safety of PFA for left atrial substrate modification in patients with long-standing persistent atrial fibrillation (AF) and macro- as well as microreentrant atrial tachycardia (AT) is scarce. Aim Here we provide a retrospective, single-centre case series regarding efficacy and safety of left atrial substrate modification, using a single-shot PFA system. Methods and Results Over a period of 6 months, 8 patients with long-standing persistent AF and AT underwent Re-PVI with left atrial substrate modification using a single-shot PFA system. Median age was 63 years (IQR 58 - 75), and 4/8 of patients were female. Time from first diagnosis of AF was 7 years (IQR 4 –10). All but 1 patient underwent previous PVI (IQR 1-3) with (5/7) or without (2/7) prior substrate modification using radiofrequency ablation. On transthoracic echocardiography, all patients showed severe left- and right-atrial enlargement, with LA volume of 58 ml/m2 (IQR 49.7–72) and RA diameter of 62 mm (IQR 55-75). In 8 patients, 9 ATs and 2 typical flutters were treated with PFA. Following PVI, additional posterior wall isolation was performed in 6/8 patients, roof in 6/8, and anterior wall (between superior mitral anulus and RSPV) in 4/8 patients. In addition, 2/8 patients had cavotricuspid isthmus ablation for typical atrial flutter. All patients received atropine prior to PVI, as well as bolus of nitro-glycerine prior to PFA of anterior wall and/or cavotricuspid isthmus. Acute success rate was 100% and all ATs as well as typical flutter terminated with PFA. After median follow-up time of 88 days (IQR 61-112), 3 patients had a documented recurrence of AF/AT, in 2 of which electrical cardioversion was necessary. We observed no acute and/or chronic complications following PFA, i.e. no pericardial effusion/tamponade, TIA/stroke, myocardial infarction, coronary artery spasm, AV-block, bleeding, or atrioesophageal fistula. Conclusion In this small, single-centre case series, left atrial substrate modification for long-standing persistent AF and AT using a single-shot PFA system was safe and showed an excellent acute success rate.

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

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

Radiomics-based multimodality prediction of left atrial appendage thrombus using coronary computed tomography angiography

Abstract Background Timely detection of thrombus in the left atrial appendage (LAA) may help guide decision-making. However, existing models have challenges in extracting comprehensive image information. It has been shown that radiomics-based prediction models can be used for accurate identification. This study investigates potential radiomic markers and constructs a highly efficient multimodality prediction model for LAA thrombus in patients undergoing coronary computed tomography angiography (CCTA). Methods We retrospectively enrolled patients with nonvalvular atrial fibrillation (NVAF) who underwent CCTA and transesophageal echocardiography (TEE) from May 2015 to May 2020. These patients were classified into thrombus or non-thrombus groups based on TEE findings. The data were balanced by resampling and assigned to training or test sets. Radiomics was conducted on the extracted features, and a random forest algorithm was employed for feature selection and importance ranking. We constructed different multimodality thrombus prediction models and compared their performance using the area under the receiver operating characteristic curve (AUC) and other efficacy parameters. Results Among 670 patients (60.17±10.98 years, 70.1% male), 5.2% (n=35) had LAA thrombi. A total of 1232 radiomics features were extracted, with 25 features selected using a random forest for modeling. Two radiomics features (Ibp_3D_m1_firstorder Skewness and original_shape_Flatness) ranked the highest. The radiomics-based multimodality prediction model achieved an AUC of 0.964 (95% confidence interval [CI]: 0.947-0.982), an accuracy of 0.926 (95% CI: 0.925-0.926), and an F1 score of 0.924, outperforming other traditional prediction models. Decision curve analysis also indicated that this model provided the best net clinical benefit. Conclusions Radiomics facilitates a comprehensive exploration of predictors associated with LAA thrombi. A radiomics-based multimodality prediction model can significantly enhance the efficiency of non-invasively detecting thrombi.Receiver operating characteristic curveDecision curve analysis

Impact of real-world off-label dose of Apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease

Abstract Background Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. Objective The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD). Methods Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban. Results Among 635 patients with AF and CKD (76.9±10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P=0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P=1.000; off-label overdose vs. standard dose, P=1.000; off-label underdose vs. off-label overdose, P=0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P=0.005). Conclusions Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.

Abnormally high plasma concentrations of M-4, the active metabolite of edoxaban, at the onset of acute kidney injury in a patient receiving rifampin and clarithromycin: a case report

BackgroundEdoxaban, the only factor Xa inhibitor with active metabolites, is metabolized by carboxylesterase-1 to its main active metabolite, M-4, which is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and is excreted in bile and urine. Because the area under the plasma concentration–time curve ratio of M-4 to parent compound is typically less than 10% in healthy subjects, M-4 is generally considered to exhibit negligible antithrombotic activity in patients treated with edoxaban. However, we identified a case in which drug interactions and kidney impairment led to a substantive increase in plasma M-4 concentrations.Case presentationThis case report involved a 68-year-old man with pancreatic cancer who was orally administered edoxaban tablets for prevention of thrombus formation in non-valvular atrial fibrillation, in addition to rifampin and clarithromycin (CAM) for treatment of mycobacterium avium complex lung disease. These medications were temporarily discontinued for a pancreaticoduodenectomy but were resumed 8 days post-surgery (POD8). On POD9, the patient developed acute kidney injury, and the trough concentrations of edoxaban and M-4 were 131.1 ng/mL and 115.8 ng/mL, respectively (M-4 ratio: 88.3%). On POD11, the M-4 trough concentration and M-4 ratio increased to 216.2 ng/mL and 186.2%, respectively. The plasma concentration of coproporphyrin-I, an endogenous biomarker of OATP1B1 activity, increased during this period.ConclusionsThis case suggests that in patients with impaired renal function taking edoxaban, co-administration of carboxylesterase-1 inducers such as rifampin and/or OATP1B1 inhibitors such as rifampin or clarithromycin may increase plasma concentrations of M-4 to clinically non-negligible levels.

Feasibility, accuracy, and reproducibility of device sizing in virtual reality for percutaneous left atrial appendage closure - a single center study

Abstract Background Left atrial appendage closure (LAAC) is a safe and effective procedure for stroke prevention in patient with non-valvular atrial fibrillation. Procedural planning and device sizing remains challenging due to the highly complex and variable three-dimensional (3D) anatomy of the left atrial appendage (LAA). Virtual reality (VR) is a innovative, recent technology allowing a superior spatial orientation visualization of 3D imaging datasets. Purpose Therefore, we aimed to evaluate feasibility and accuracy of LAA measurements in VR for device sizing in patients planned for LAAC. Methods Twenty-one patients (79±7 years, 62% male) with non-valvular atrial fibrillation scheduled for LAAC were randomly included in our study. Preprocedural a multi-slice computed tomography (MSCT) was performed for device sizing in all patients. MSCT-based 3D models were established and visualized in VR using a dedicated software (VMersive, Warsaw, Poland). LAA dimensions (Ostium, landing zone (LZ), and depth) were assessed directly in the virtual environment. Conventional measurements of LAA ostium, landing zone (LZ) and depth using commercially available software were compared to measurements in VR. Results 3D reconstruction of MSCT datasets and visualization in VR were successfully performed automatically in all patients within a few seconds. MSCT and VR demonstrated good correlations for ostium minimum (r = 0.93), maximum (r = 0.8) and mean (r = 0.88, all p<0.001) diameters. Additionally, LZ minimum (r=0.84), maximum (r=0.86) and mean (r=0.9) diameters showed good correlation (all p<0.001). Moderate correlation was observed for depth measurements (r=0.76, p<0.001). Furthermore, intraclass correlation coefficients ranging from 0.88 to 0.98 denoted high inter- and intraobserver agreement. Conclusion Immersive VR allows highly feasible, accurate and reproducible measurements of the LAA dimensions directly in the virtual environment, hence enabling accurate device sizing for LAAC.

Sinus rhythm maintenance and the changes of echocardiographic parameters in patients with late persistent atrial fibrillation at 6 months after direct current cardioversion

Abstract Background Late persistent non-valvular atrial fibrillation (AF), with a duration of its episode ≥90 days and up to 12 months, is considered a distinct persistent AF entity, which might possess substantial differences as compared to its early persistent pattern (up to 3 months) in terms of myocardial remodeling and its reversibility after cardioversion. Purpose To study the changes of echocardiographic parameters in patients with non-valvular late persistent AF with respect to sinus rhythm (SR) maintenance at 6 months after successful direct current cardioversion (DCCV). Methods The cohort single-center study enrolled 59 late persistent AF patients, who underwent a successful elective DCCV. At 6-months follow-up, patients were subdivided into the groups regarding SR maintenance: 32 (54 %%) patients with a maintained SR (G1), and 27 (46 %) patients with a failure to maintain SR (G2). The parameters of myocardial remodeling and function were evaluated by transthoracic (TTE) and transesophageal echocardiography (TEE) baseline (by TTE and TEE) and at 6-months follow-up (by TTE). Results TTE data from G1 patients, in contrast to G2, suggested better baseline status of left heart chambers, particularly the lower diameter of left atrium (LA), left ventricular (LV) end-diastolic and end-systolic volumes and higher LV systolic function (by LV ejection fraction [EF]). According to the TEE data, G2 (vs. G1) was characterized by more prevalent cases of LA spontaneous (echo) contrast (41 % vs. 15 %, respectively; p=0,042) and LA appendage flow velocity ≤40 cm/s (82 % vs. 53 %, respectively; p=0,022). At 6-months follow-up TTE, G1 patients, as opposed to G2, demonstrated a better profile of echocardiographic parameters, namely a lower LA diameter, LA and right atrium (RA) volumes, along with less advanced LV remodeling and higher LV EF. TTE data from G1 at 6-months follow-up after DCCV suggested the reverse remodeling of both atria, namely the decrease of LA diameter, LA volume and its index (Fig. 1), as well as RA volume and its index. Moreover, G2 demonstrated a decline in LV systolic function, in particular the rise of LV end-systolic volume and decrease of LV EF (Fig. 2), as compared to G1. Furthermore, at 6-months follow-up, G2 patients presented with more advanced severity of PH and tricuspid regurgitation, in comparison with G1. Conclusions Late persistent AF patients with a SR maintenance at 6-months follow-up after successful DCCV presented a better baseline profile of myocardial remodeling and systolic function. The SR maintenance at 6-months follow-up after DCCV was associated with the reverse remodeling of left heart chambers (LA and LV) and RA. On the contrary, a failure to maintain SR in late persistent AF patients was associated with a deterioration in LV systolic function, and more advanced PH and tricuspid regurgitation.

Cognitive behavioral therapy for symptomatic paroxysmal atrial fibrillation: effects on physical activity, sleep and heart rate variability

Abstract Background We have devised a novel psychological intervention, cognitive behavioral therapy for paroxysmal atrial fibrillation (AF-CBT), that targets symptom preoccupation and avoidance behaviour. AF-CBT significantly improved cardiac anxiety and quality of life (QoL) in a randomized trial. To what extent this may be attributed to changes in physiological parameters is yet to be determined. Purpose A) to assess changes in objective and subjective measures of physical activity and sleep. B) to evaluate potential treatment effects on heart rate variability (HRV). Methods Patients with paroxysmal AF on optimal medical therapy (65.4±8.3 years, 58% women) and European Heart Rhythm Association Symptom Score ≥2b were randomized to a 10-week therapist-led online AF-CBT (n=65) or a control group (n=62), with the primary outcome of Atrial Fibrillation Effect on Quality-of-life (AFEQT). A Patch-Holter with an integrated accelerometer was applied for five days at baseline, post-treatment, and at three months follow-up. Each recording was divided into day and night (sleep time) based on posture, heart rate, and activity. HRV was analysed in both time and frequency domains, excluding AF episodes and aberrant beats. Results AFEQT increased from 62.4±14.3 to 83.7± 13.8 points in the AF-CBT group at the 3-month follow-up with a relative difference of 15.0 points. At baseline, the participants walked 8040±2600 steps/day and slept 8.0 ± 1.1 hours. AF-CBT did not increase physical activity, and there were no significant changes in objective sleep duration. The Insomnia Severity Score went from subclinical (12.2±6.7) to near normal values (8.1±5.6), which was significant as compared to controls (p=0.032). AF burden increased from 5.3% to 7.3% in the AF-CBT group and 5.0% to 9.2% in the control group, with no difference between the groups (p=0.59). We did not observe any change in heart rate or HRV indices at rest during the day or at night. Conclusion AF-CBT did not mediate its effects on QoL by improving objective physiological variables. Thus, our findings underline the importance of subjective, psychological, and behavioural aspects and indicate that AF-CBT might fill a void beyond medical and lifestyle interventions in comprehensive AF care.

Optimal anticoagulant strategy for periprocedural management of atrial fibrillation ablation: a systematic review and network meta-analysis

Abstract Background This network meta-analysis was performed to rank the safety and efficacy of periprocedural anticoagulant strategies in patients undergoing atrial fibrillation ablation. Methods MEDLINE, EMBASE, CENTRAL, and Web of Science were searched to identify randomized controlled trials comparing anticoagulant regimens in patients undergoing atrial fibrillation ablation up to July 1, 2021. The primary efficacy and safety outcomes were thromboembolic and major bleeding events, respectively, and the net clinical benefit was investigated as the primary-outcome composite. Results Seventeen studies were included (n = 6950). The mean age ranged from 59 to 70 years; 74% of patients were men and 55% had paroxysmal atrial fibrillation. Compared with the uninterrupted vitamin-K antagonist strategy, the odds ratios for the composite of primary safety and efficacy outcomes were 0.61 (95%CI: 0.31–1.17) with uninterrupted direct oral anticoagulants, 0.63 (95%CI: 0.26–1.54) with interrupted direct oral anticoagulants, and 8.02 (95%CI: 2.35–27.45) with interrupted vitamin-K antagonists. Uninterrupted dabigatran significantly reduced the risk of the composite of primary safety and efficacy outcomes (odds ratio, 0.21; 95%CI, 0.08–0.55). Conclusion Uninterrupted direct oral anticoagulants are preferred alternatives to uninterrupted vitamin-K antagonists. Interrupted direct oral anticoagulants may be feasible as alternatives. Our results support the use of uninterrupted direct oral anticoagulants as the optimal periprocedural anticoagulant strategy for patients undergoing atrial fibrillation ablation.

Phenotype groups in atrial cardiomyopathy and their prognosis

Abstract Background Atrial cardiomyopathy (ACM) includes patients with heterogenous demographic characteristics and comorbidities. Defining phenotype groups with similar clinical characteristics is important for the effective treatment of these patients, and for their prognosis and prevention of ACM. Purpose To conduct a cluster analysis that could help us in phenotyping ACM and exploring the clinical complexity of this entity. Methods We performed a hierarchical cluster analysis based on Ward’s Method using 10 clinical binary variables (hypertension, diabetes mellitus, heart failure, obesity, chronic obstructive pulmonary disease, cancer, coronary artery disease, sinus node dysfunction or atrio-ventricular block, implanted pacemaker, and ischemic stroke), identifying the optimal number of clusters. We investigated differences in demographic, laboratory and echocardiographic parameters, and treatment between defined clusters, and assessed the impact of these factors on prognosis. Results Of 724 evaluated consecutive patients with dilated left atrium only 200 met the criteria for advanced atrial cardiomyopathy, defined as severely dilated left atrium with volume index (LAVI) ≥ 48 ml/m2, preserved left ventricular systolic function - ejection fraction ≥ 50%, without an overt valvular or ventricular disease, and were included in the analysis. Mean age of the studied population was 73.91 ± 9.74 years, 58 % of them were women. We identified 4 clusters: cluster 1 (n = 73, 36%) were younger overweight patients with paroxysmal atrial fibrillation (AF); cluster 2 (n = 56, 28%) - old patients with congestive heart failure (CHF) and low body mass index (BMI); cluster 3 (n = 34, 17%)- diabetic patients with obesity and CHF; and cluster 4 (n = 37, 19%) old patients with tachycardia-bradycardia syndrome, implanted pacemakers, and long -standing AF. Over a mean follow up of 20.6 months cluster 2 had the highest mortality rate (28.6%), followed by cluster 3 (20.6%), compared to the lower mortality rate of cluster 1 and 4 (11% and 10.8%, respectively, p=0.047). The presence of heart failure (HR 4.4, CI 1.5 ÷12.7, p=0.006), cancer (HR 3.3, CI 1.6 ÷ 6.9, p=0.002) and greater than moderate tricuspid regurgitation (HR 5.4, CI 2.6 ÷ 11.3, p<0.001) were predictors of poor outcome. Conclusion In patients with advanced atrial cardiomyopathy, four main clusters were identified, differentiated by distinct comorbidities. Both clinical and echocardiographic parameters were found to be associated with an increased risk of mortality.Phenotype clusters of ACMKaplan-Meier curves of clusters

Mavacamten in a real-world hypertrophic cardiomyopathy population: how many may be eligible?

Abstract Introduction Mavacamten is a newly approved drug for obstructive hypertrophic cardiomyopathy (oHCM) and is currently being studied in non-obstructive HCM (nHCM). Our goal was to evaluate how often patients with oHCM and nHCM in a real-world cohort would be eligible for the main mavacamten trials: EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM. Methods Single-centre retrospective study enrolling consecutive patients with confirmed HCM, as per the 2023 ESC Guidelines, with at least yearly follow-up in our center, from 2017-2023. Key inclusion criteria from the three trials were considered: NYHA class II-III for all; obstructive forms (defined as peak left ventricle outflow tract [LVOT] gradient ≥50 mmHg at rest, after Valsalva manoeuvre or exercise) for EXPLORER-HCM and VALOR-HCM; left ventricular ejection fraction (LVEF) ≥55% for EXPLORER-HCM and MAVERICK-HCM; LVEF ≥60% and formal criteria for septal reduction therapy for VALOR-HCM, and NT-proBNP ≥300pg/mL for MAVERICK-HCM. Key exclusion criteria (estimated glomerular filtration rate [eGFR] <30mL/kg/1.73m2, QTc using the Fridericia’s formula >500ms, paroxysmal or intermittent atrial fibrillation present on screening electrocardiograph) were also considered. Results Overall, 410 patients were diagnosed with HCM, of whom 361 (88%) were alive at follow-up and included in the analysis: mean age of 63 ± 16 years, 196 (54%) were male, 272 (75%) with septal HCM and 60 (17%) with oHCM. According to the criteria of EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM, 35 (10%), 6 (2%) and 27 (7%) patients would be eligible for enrolment, respectively. In patients with oHCM, 35 (58%) would be eligible for the EXPLORER-HCM trial. In the overall cohort, 65 (18%) would have criteria for at least one of the trials. The main reasons for exclusion were as follows: 191 (53%) NYHA I, 43 (12%) with NYHA IV, 12 (3%) had a LVEF <55%, 8 (2%) had both HCM and infiltrative myocardial disease and/or moderate-to-severe aortic stenosis and 8 (2%) had an eGFR <30mL/kg/1.73m2. In patients with nHCM, 16 (5%) would have been excluded due to NT-proBNP <300pg/mL and 8 (3%) due to paroxysmal atrial fibrillation. Conclusion In a real-word HCM cohort, we found that approximately 1 in every 5 patients would have criteria for either of the mavacamten trials, with more than half of oHCM being potential candidates for the EXPLORER-HCM. The main reasons for non-eligibility were NYHA I and LVEF <55%.

Targeting ventricular tachycardia originating from the anterolateral papillary muscle with stereotactic body radioablation therapy

Abstract Background Ventricular Tachycardia (VT) is prevalent in the setting of non-ischaemic cardiomyopathy (NICM), a heterogeneous group of conditions characterized by myocardial dysfunction in the absence of coronary artery disease. Challenges of catheter ablation to treat VT in NICM patients are well known, and recurrence rates can be as high as 58%. Stereotactic body radioablation therapy (SBRT) involves precise delivery of radiation to arrhythmogenic substrates, and represents a novel treatment to reduce recurrent implantable cardioverter defibrillator (ICD) therapies in patients with refractory VT. Though SBRT has shown preliminary effectiveness in reducing VT episodes, its effectiveness in NICM patients has not been widely evaluated. Purpose To evaluate SBRT effectiveness in NICM patients with scars at the basal anterolateral papillary muscle at a tertiary care center between November-December 2022. Methods Eligible patients had their VT substrate mapped using a single-use ECGI vest and a 4D-CT simulation scan. In addition, MRI scans were used to aid anatomical identification of the anterolateral papillary muscle which could not be seen on the non-contrast diagnostic CTs. SBRT was delivered in a single fraction of 25 Gy under image guidance. Effectiveness of the treatment was evaluated as changes in frequencies of total antitachycardia pacing (ATP) and ICD shock episodes from 6 months pre-, and within to 3, 6, and 12 months follow up post SBRT. Results Participants were 3 males with NICM, aged 56, 60, and 73 with previous dual chamber ICD implantation, 2 of whom had a history of VT ablation/ VT storm and paroxysmal atrial fibrillation. All participants had basal lateral scar, and were receiving beta blockers, mexiletine, and amiodarone with refractory VT before SBRT treatment. Prior to SBRT, ICD device interrogation showed a total of 119 (77, 7, and 35 in patients 1-3 respectively) ATPs, and 27 (10, 1, and 16 in patients 1-3 respectively) ICD shocks delivered. At 12 month follow-up, none of the participants experienced any episodes of ATP or ICD shock. Ejection fraction remained consistent pre-post SBRT. Conclusion SBRT showed remarkable success in reducing ATP and ICD shock episodes, facilitating uncomplicated 1 year follow-up in 3 male patients with NICM and VT from the anterolateral papillary muscle.

A novel bionic constructional left atrial appendage occlude device: the result of preclinical experiment and first-in-human study

Abstract Objectives Left atrial appendage occlusion (LAAO) has emerged as a viable substitute for oral anticoagulation (OAC) for stroke prevention among individuals with atrial fibrillation (AF) these years. The high variability of left atrial appendage (LAA) in different individuals would lead to failure of LAAO or significant PDL post procedure using the existing occluders. Therefore, novel occluder which could address these issues is of great urgent. Methods SimuLock® occluders were implanted in 18 healthy canines percutaneously. Angiography and transesophageal echocardiography were employed to evaluate the effect of closure. The canines were sacrificed post-procedure immediately or on 30th, 90th and 180th. Subsequently, the gross anatomy was examined and endothelialization of device surface was evaluated by HE staining. 3 patients who had non-valvular AF and underwent LAAO in Zhongshan hospital, Fudan University using SimuLock® were enrolled in this study. They all had a follow-up of 3 months. Results All animals were implanted with the SimuLock® device. In 27.8% of animal cases, a LAA occluder of the "large umbrella and small disc" type which could adapt to LAA morphology well was employed, and all surpassed the specifications of existing occluders. None of residual shunt was observed all canines in 180 days post procedure. In addition, none adverse events were documents during the 6-month follow-up. In the first-in-human study, the SimuLock® occluder were successfully implanted in 3 subjects, all subjects achieved complete occlusion, without residual shunt > 3mm. The incidence of major adverse events, operation-related serious adverse events and device-related serious adverse events in all subjects were not documented in 3 months after operation. Conclusions In the animal experiment and first-in-human study, SimuLock® device showed the ability of adapting to various LAA morphology well and rapid endothelialization. The utilization of SimuLock® for LAAO exhibited high efficacy and safety.Central figure

Efficacy and safety of catheter ablation for paroxysmal atrial fibrillation as first-line therapy vs. after drug failure -analysis from Japan Nationwide Ablation (J-AB) Registry-

Abstract Background Catheter ablation is an effective rhythm control therapy for atrial fibrillation (AF). Recent advancements in technology have improved the efficacy and safety of this procedure. Current European Society of Cardiology and Japanese Circulation Society guidelines recommend that catheter ablation (CA) for patients with paroxysmal AF (PAF) after failure of drug therapy is classified as Class I, and CA as first-line therapy is categorized as Class IIa. However, there are limited clinical studies directly comparing these groups. Objective This study aimed to compare the efficacy and safety of CA as first-line therapy vs. those after failed drug therapy using data from the Japan Nationwide Ablation (J-AB) Registry led by the Japanese Heart Rhythm Society. Methods Detailed data of patients who underwent catheter ablation for PAF extracted from the J-AB registry were analyzed. Patients were divided into two groups: those who underwent CA as first-line therapy (First-line group) or those who underwent CA after failed drug therapy (Drug failure group). Patients’ characteristics, efficacy and safety of CA were compared between the two groups. Efficacy was assessed by evaluating the recurrence rate of any atrial arrhythmia within one year after the 90-day blanking period, and major safety outcomes were set as severe bleeding complication, stroke, and gastrointestinal disorders during the perioperative period. Result This analysis included 5,011 cases with a median age of 69 years (range 61-75) and 35% females. Comparing patient characteristics between the first-line therapy group (n = 3,447) and the drug failure group (n = 1,564), there are no statistically significant differences between the two groups except in left atrium diameter in echocardiogram (LAD) (38 [34-42] mm vs. 38 [34-43] mm, P <0.001), serum creatinine levels (0.8 [0.7-1.0] mg/dl vs. 0.9 [0.7-1.0] mg/dl, P <0.001), and beta-blocker usage (38.2% vs. 46.7%, P <0.01). A total of 501 recurrence events were observed in this analysis during a median follow-up of 365 [254-390] days. Recurrence rates did not statistically differ between the two groups (log-rank P=0.49). After adjusting for contributing factors with age, gender, body mass index, LAD, and left ventricular ejection fraction in echocardiogram using a multivariate Cox proportional hazards model, efficacy outcomes showed no significant difference between the two groups (adjusted hazard ratio; 1.06 95% confidence interval; 0.88-1.28, P = 0.55). Besides, the two groups had no significant difference in major safety outcomes. Conclusions Catheter ablation as the first-line therapy for paroxysmal atrial fibrillation showed a similar recurrence rate of atrial arrhythmias and adverse events compared to those who underwent catheter ablation after drug failure.

Cardiovascular disease history as a predictor for adverse outcomes in frail older adults admitted to acute geriatric settings: 12-month outcomes from an Australian frailty registry

Abstract Introduction Frailty is common in older adults with cardiovascular disease (CVD), with prevalence between 25-62% (1). The incidence of CVD increases with age, yet the outcomes of frail older adults with a history of CVD who present to acute geriatric settings, is not well understood. Purpose To report the association of CVD and rehospitalisation and/or mortality at 12 months in a cohort of frail older adults enrolled in an Australian frailty registry. Methods A convenience sample of participants enrolled in the frailty registry, with 12-month follow-up completed. The frailty registry is a prospective cohort study of adults admitted to the rehabilitation and aged care departments at two Australian hospitals. Frailty was assessed using the Clinical Frailty Scale (CFS), a score of 1-4 is ‘non-frail’, 5-6 is ‘mild-moderately frail’ and 7-9 is ‘severely frail’ (2). For this study, ‘CVD’ was defined as having a history of either heart failure, stroke, or atrial fibrillation. The cumulative incidence of first rehospitalisation and/or death during the first 12 months post discharge was estimated using one minus the Kaplan-Meier estimate of the survival function. Association between CVD (history of CVD, and type of CVD condition) and the composite endpoint were analysed. Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox models incorporating variables of interest and potential confounders. Results A total of 592 participants were included, median age was 82 years, 59% (n= 349) were female. The majority were frail with 50% (n= 295) classified as mild-moderately frail and 21% (n= 123) classified as severely frail. Almost half (45%, n= 265) had a history of CVD. The incidence of frailty (CFS score ≥5, mild-severely frail) was higher in those with CVD compared to those without CVD (76% vs 66%). A history of CVD was significantly associated with higher rate of first readmission or death within 12 months, compared to no history of CVD (p=0.017) (Figure 1). Of the three CVD conditions, heart failure was the only independent predictor of the composite endpoint (HR 1.60 [CI 1.14 -2.24], p=0.007). A CFS score of mild-moderately frail (HR 1.51 [CI 1.18 - 1.93, p=0.001) and severely frail were also independent predictors of the composite endpoint (HR 1.83 [CI 1.35- 2.48], p=<0.001) (Table 1). Conclusions A history of CVD has a significant impact on adverse outcomes in frail older adults admitted to acute geriatric settings. Frailty according to the CFS was independently predictive of rehospitalisation and mortality in this cohort. Heart failure was the only independent predictor of the composite endpoint. These findings underscore the importance of identifying and addressing CVD and in the context of frailty, emphasising the need for targeted interventions to improve outcomes in this vulnerable population.Figure 1.Table 1.

Neurodegeneration is highly associated with comorbidity burden in HFrEF patients

Abstract Background Heart failure (HF) is associated with cognitive decline and risk for dementia. Blood levels of amyloid beta 40 and 42 (Aβ40, Aβ42), tau protein (tau), and neurofilament light chain (NfL) have been found to be altered in neurodegenerative disease. Previous research has established a clear association between these neuromarkers and the risk of developing cognitive dysfunction and mortality in the general population. Objective The aim of this study was to investigate the association between the respective neuromarkers and comorbidity burden, as well as to explore whether comorbidity burden impacts the relationship between neuromarkers and outcome in HF patients. Methods Plasma levels of Aβ40, Aβ42, tau, and NfL were quantified using a single-molecule array assay. The primary outcome parameter was all-cause mortality. Results A total of 470 HFrEF patients were enrolled in the study, with a median age of 62 years (IQR: 52–72); 77% were male. Median NT-proBNP concentration was 1812 pg/ml (IQR: 718–3881). Elevated levels of all biomarkers were closely associated with comorbidity burden (Figure 1). All neuromarkers showed increased levels in individuals with chronic kidney disease (CKD) and known carotid artery stenosis (CAS), except for Aβ40, which did not show significant elevation in CAS (NfL: p<0.001 for both; t-tau: p<0.001 and p=0.041; Aβ40: p<0.001 and p=0.050; Aβ42: p<0.001 and p=0.033, respectively). In patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), only NfL levels were significantly elevated (p<0.001 for both), whereas atrial fibrillation (AF) was associated with higher levels of NfL and t-tau (p<0.001 for both). In individuals with iron deficiency, only Aβ42 levels were significantly higher (p=0.025). All biomarkers showed significant associations with all-cause mortality [crude HR for an increase in 1-log unit (95%CI): NfL 4.44 (3.02-6.53), t-tau 5.04 (2.97-8.58), Aβ40 3.90 (2.27-6.72), Aβ42 5.14 (2.84-9.32); p<0.001 for all] (Figure 2). These associations remained statistically significant after adjusting for comorbidity burden including AF, T2DM, CAD, CKD, CAS and ID [adjusted HR for an increase in 1-log unit (95%CI): NfL 3.28 (1.93-5.57), t-tau 3.96 (2.07-7.57), Aβ40 2.42 (1.34-4.38), Aβ42 3.05 (1.56-5.97); p<0.01 for all]. Conclusion The findings suggest a close connection between elevated levels of markers of neurodegeneration and increased comorbidity burden in HFrEF patients. While this association may indicate the cumulative risk leading to neuronal injury and HFrEF progression, a causal relationship cannot be excluded. The observed accelerated neurodegeneration in HFrEF underscores the need for further investigation into this complex interplay.Figure 1Figure 2

Real-world evidence of implanting leadless pacemakers after transcatheter aortic valve implantation procedures

Abstract Background Conduction disturbances can be a complication of Transcatheter Aortic Valve Implantation (TAVI) procedures, for which transvenous pacemakers (TVPs) are recommended. Leadless pacemakers (LPs) are a safe alternative to TVPs in a pacemaker-indicated population, but little is known about their use for TAVI-related conduction disturbances. Purpose To examine rates of pacemaker implantation post-TAVI, compare complications, all-cause mortality, and ventricular pacing rates in LP vs. TVP patients, and assess pacemaker deactivations/upgrades in LP patients. Methods Data from Optum’s de-identified Clinformatics Data Mart Database linked to a device registry between 2016 and 2021 were used to identify patients with TAVI procedures that are subsequently implanted with an LP or a TVP. Claims data were used to assess complications and all-cause mortality; device-reported parameters were used to calculate VP rates and deactivations. Complication rates, all-cause mortality, ventricular pacing rates, and device deactivations were calculated for patients with a pacemaker implant between 7 days before and 90 days after TAVI. Chronic complication rates, defined as complications with the potential to occur outside the acute peri- or post-procedural period, were assessed at 1 year. Regressions were used to compare complications and all-cause mortality, adjusting for patient characteristics. Results In a cohort of 18,073 patients with a TAVI procedure, 11.7% were implanted with a pacemaker at 1 year post-TAVI; 76.7% of implants occurred within 7 days. LPs comprised 7.2% of the total pacemaker implants observed. Of those LPs in the registry, around 25% have VDD capability. LP patients were older (avg. 84 LP, 82 TVP, p=0.02) and were more likely to have atrial fibrillation, end-stage or chronic kidney disease, and ventricular arrhythmias. Of patients implanted with a pacemaker within 90 days post-TAVI (LP N=122, TVP N=1,779), there were no differences in 30-day complication rates (12.3% LP, 15.6% TVP, unadj. p=0.33, adj. p=0.27). LP had fewer chronic complications than TVP (0.8% LP, 9.4% TVP, unadj. p=0.02, adj p=0.02) though the sample size was small. LP patients had higher unadjusted 30-day all-cause mortality (4.1% LP, 1.0% TVP, unadj. p=0.01, adj. p=0.06), reflecting the higher acuity of LP patients. At both 30 days and 1 year post-implant, most patients (85.3% LP, 72.7% TVP) continued to receive pacing support (ventricular pacing >10%). TVP patients were more likely than LP patients to be pacing dependent (ventricular pacing ≥90%) at both 30 days (53.8% vs. 29.4%) and 1 year (44.7% vs. 35.7%) post-implant. There were no observed deactivations/upgrades in LP patients at 1 year. Conclusion LPs, when used concomitantly with TAVI procedures, show similar acute and lower chronic complication rates compared to patients treated with TVPs implanted with TAVI. Most patients who received a pacemaker post-TAVI continue to receive pacing support.Acute and Chronic complicationsVentricular pacing