Atrial Fibrillation Patients Research Articles

Role of CT-derived global longitudinal strain in identifying left ventricular dysfunction in patients with severe aortic stenosis and preserved left ventricular ejection fraction

Abstract Introduction In patients with severe aortic stenosis, LVEF <50% is a current class 1 indication for aortic valve replacement. There are however studies showing increased mortality in patients with asymptomatic severe aortic stenosis and LVEF between 50-59% [1, 2]. Global longitudinal strain (GLS) has emerged as a more sensitive predictor of systolic dysfunction than ejection fraction in a wide number of cardiac diseases [3]. Purpose The aim of our study was to analyze left ventricular global longitudinal strain (GLS) by cardiac computed tomography (CT) in patients with severe aortic stenosis. We hypothesized that a larger portion of patients with LVEF 50-59% have signs of systolic dysfunction by GLS as compared to patients with LVEF ≥60%. Methods We identified 238 patients (median age 81, 51.3% females) with severe aortic stenosis, assessed by cardiac CT before undergoing transcatheter aortic valve replacement at Uppsala University hospital between 2016-2019. Patients in atrial fibrillation was excluded due to suboptimal image quality. Left ventricular mass index (LVMi), EF and peak GLS were calculated. The patients were divided into three groups based on LVEF (Reduced LVEF <50%, Low-Normal LVEF 50-59% and Normal LVEF ≥60%) and compared with each other regarding GLS, biomarkers and background variables. The cut off for significantly reduced GLS was set at <16%, in accordance with recently proposed criteria [4]. Results As expected GLS was significantly reduced in all patients with LVEF <50%. Among patients with Low-Normal LVEF, 62.3% had significantly reduced GLS as compared to only 3.8% patients with Normal LVEF >60% (p < 0.001). Median GLS in Low-Normal LVEF was 15.5% (IQR 14.1 - 17.4) as compared to 20.2% (IQR 18.4 - 21.9) in Normal LVEF (p < 0.001). Patients with Low-Normal LVEF had a significantly higher LV mass as compared to patients with Normal LVEF (median LVMi 85.8 g/m² vs. 75.8 g/m², p < 0.001). NT-pro-BNP was significantly higher in patients with Low-Normal LVEF compared to Normal LVEF (median 1130 vs. 664 ng/l, p = 0.003). Conclusions Almost two third of patients with severe aortic stenosis and lower range of normal LVEF (50-59%) had abnormally reduced GLS, reflecting systolic LV dysfunction, which was uncommon among those with LVEF >60%. Patients with LVEF 50-59% also presented with higher LV mass index and higher levels of NT-pro-BNP than patients with normal LVEF >60%, reflecting hypertrophic response of the myocardium to pressure overload which over time may lead to progressive myocardial decompensation. LVEF in the range of 50-59% might be an early sign of LV decompensation in severe aortic stenosis.

The effect of metformin use on the risk of atrial fibrillation in patients with type 2 diabetes: data from the UK biobank

Abstract Objective The present study aims to investigate the protective role of metformin against atrial fibrillation (AF) and stroke in type 2 diabetes (T2DM) patients treated with other antidiabetic medications. Methods We included 10,011 participants with T2DM from the UK biobank database, with a follow-up for new diagnoses of AF and stroke recorded until 2023. We employed logistic regression analysis and competing risk models to assess the association between metformin use and the incidence of AF or stroke. Results The cross-sectional analysis revealed that, compared with the use of other antidiabetics, metformin was associated with a lower prevalence of AF (odds ratio [OR] 0.71, 95% CI: 0.57–0.89) and stroke (OR 0.70, 95% CI: 0.56–0.86). In the competing risk model, compared to other antidiabetics, metformin may reduce the risk of AF (sub-hazard ratio [SHR] 0.86, 95% CI: 0.75–0.98) and stroke (SHR 0.62, 95% CI: 0.44–0.86) (Figure 1). Subgroup analysis indicated a significantly lower incidence of AF or stroke in patients under 65 years of age (SHRs were 0.80, 95% CI:0.67-0.96 for AF and 0.52, 95% CI: 0.34-0.81 for stroke) and in female patients (SHRs were 0.65, 95% CI:0.52-0.81 for AF and 0.53, 95% CI: 0.30-0.91 for stroke). Notably, metformin significantly reduced the incidence of AF in non-insulin users (SHR 0.80, 95% CI: 0.66-0.97) and the incidence of stroke in insulin users (SHR 0.55, 95% CI: 0.35-0.87) (Figure 2). Conclusion Our findings suggest that metformin use, in comparison to other antidiabetic medications, is associated with a reduced risk of AF and stroke, especially in non-insulin users for AF and insulin users for stroke.

Left atrial cardiomyopathy predicts stroke recurrence and atrial fibrillation

Abstract Background Markers of atrial cardiomyopathy, encompassing both left atrial (LA) structure and function, have been linked to an increased long-term risk of ischemic stroke and atrial fibrillation (AF). However, the short-term risk associated with these markers in patients with stroke without previously known or detected AF during stroke workup remains insufficiently characterized. Purpose To investigate the association between functional and structural markers of atrial cardiomypathy using cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) in patients with stroke of either i) undetermined etiology or ii) small or large-vessel stroke and the recurrence of stroke or new-onset AF. Methods Between 2019 and 2021 we consecutively included 91 patients with a recent stroke (<30 days) without known or detected AF during at least 48-hours of continuous monitoring. All patients had CMR with LGE to determine LA emptying fraction, LA volumes, and LA fibrosis. The primary endpoint was a composite of stroke recurrence or new-onset AF. Results Baseline characteristics are presented in Table 1. Over a median follow-up of 2.3 years, fourteen patients (15%) reached the combined endpoint of stroke or new-onset AF. Multivariable cause specific regression analysis demonstrated that a lower LA emptying fraction was associated with the primary endpoint (hazard ratio [HR], 1.41 per 5% decrease [95% CI, 1.09–1.82]). LA volumes and LA fibrosis did not show any associations with the combined endpoint (Table 2). Subgroup analysis indicated that the results were predominantly driven by new-onset AF in patients with stroke of undetermined etiology Conclusion Our results suggests that LA emptying fraction, measured using CMR, may serve as a prognostic indicator for stroke recurrence or new-onset atrial fibrillation in patients without detected AF, especially in those with stroke of undetermined etiology. Surprisingly, LA fibrosis was not associated with either recurrence of stroke or new-onset AF.

Novel role of human epicardial adipocyte-derived SPARCL1 in suppression of postoperative atrial fibrillation in patients undergoing cardiovascular surgery

Abstract Background Postoperative atrial fibrillation (POAF) occurs in 20-50% after cardiovascular surgery and is associated with the short and long-term morbidity/mortality. The epicardial adipose tissue (EAT) may have a potential role to regulate the incidence of POAF. Purpose We explored the possible role of human epicardial adipocyte-derived adipokines in the regulation of the myocardial redox state and POAF. Methods We prospectively evaluated 149 patients without known AF who underwent scheduled open-heart cardiovascular surgery between May 2020 and November 2022. They were divided into POAF or Non-POAF group and followed up after discharge (476.6 ± 290.0 days). POAF was defined as AF lasting more than 30 seconds after the surgery. Human EAT samples were obtained from these patients during surgery and the preadipocytes were isolated. Preadipocytes were terminally differentiated to mature adipocytes and mRNAs were extracted. Genome-wide expression profiling of 6 vs. 6 matched samples of the POAF and Non-POAF groups was performed using Microarray analysis, and the results were validated with qPCR in all the cohort samples. The effects of secreted adipokines on the cardiomyocytes were assessed in terms of oxidative stress. Superoxide and whole reactive oxygen species (ROS) were evaluated with luminometry and live-cell fluorescent probes respectively. As the oxidative stress associated signalling, the phosphorylation of ERK and p38-MAPK were evaluated with western blotting. Angiotensin II (Ang-II) was used to induce oxidative stress and phosphorylation of MAPK. Results POAF was observed in 53 patients (36%). Microarray analysis (n = 6) revealed that there were 132 down- or up-regulated cording genes in epicardial adipocytes of the POAF group compared to the Non-POAF group. Of these genes, 11 genes cording secretable molecules were validated by qPCR (n = 69), showing that only SPARCL1 had significantly downregulated in the POAF group compared to the Non-POAF group (P = 0.005). Superoxide and ROS were induced by Ang II (P < 0.01) and attenuated by SPARCL1 dose-dependent manner (P < 0.01) in neonatal rat cardiomyocytes. The phosphorylation of ERK and p38-MAPK were induced by Ang II (P < 0.01) and attenuated by SPARCL1 (P < 0.01) dose-dependently. Co-culture of human induced pluripotent stem cell-derived atrial cardiomyocytes (iPS-ACM) and human epicardial adipocytes revealed that the adipocytes derived from Non-POAF group suppressed the superoxide (P = 0.002) and ROS (P = 0.02) in iPS-ACM compared to POAF group. Kaplan-Meier survival analysis revealed that the POAF group (P = 0.01) and low SPARCL1 expression in epicardial adipocytes (P = 0.018) were associated with a higher incidence of long-term adverse cardiovascular events after surgery. Conclusion: SPARCL1 derived from epicardial adipocytes may play an important role in the suppression of POAF and long-term cardiovascular events via improving the myocardial redox state.

Procedural findings and follow-up results of catheter ablation of atrial fibrillation in patients after radiation therapy for breast cancer

Abstract Backround Data on breast cancer radiation therapy (RT) associated atrial cardiomyopathy and its potential role in the pathophysiology of atrial fibrillation (AF) is very limited. Objectives To investigate the effect of breast cancer radiotherapy (RT) on atrial cardiomyopathy and its possible role in the pathophysiology of atrial fibrillation. What is the therapeutic success of antral pulmonary vein isolation (PVI) with possible substrate modifications (CFAE) in patients with breast cancer radiation therapy and paroxysmal or persistent atrial fibrillation. Methods We searched the institution’s data base for patients who received RT for breast cancer and underwent subsequently 3D mapping guided AF ablation. Intraprocedural mapping data and short- and long-term results of ablation were evaluated according to "no low voltage" and "low voltage" present. Low voltage amplitudes in bipolar electrograms were defined as <0.5 mV for endocardial maps created during SR and <0.3mV during AF. Ablation strategy comprised pulmonary vein isolation (PVI) ± additional substrate modification according to the mapping results. Follow Up (FU) was evaluated using repetitive 7-days Holter ECG and clinical visits. Results We included 45 patients (all female, 70.9±7.2 years) with paroxysmal or persistent AF (n=18 and n=27). In 3D mapping, 60% of the patients (27/45) showed left atrial low voltage (LV group) with the majority showing low voltage in the anterior wall of the left atrium (LA) in 18 of 45 patients (40%). PVI with ablation of complex fractionated signals (CFAE) was predominantly performed (18/27). After one ablation, 33.3% (9) of the patients in the LV group were recurrence-free and after an average of 1.9 ablations, freedom from recurrence was achieved in 21 patients with low voltage (77.8%). In 18 patients, no low voltage was detected (NLV group) and PVI only was performed in the majority (14/18). In this NLV group, 61.1% (11) of the patients were recurrence-free after one ablation and freedom from recurrence was achieved in 72.2% (13) after an average of 1.2 ablations. Conclusion Thoracic radiation therapy in patients with breast cancer can lead to low voltage in the LA with the predominant low voltage location being the anterior wall of the LA. An extended ablation strategy (PVI & CFAE) can show good treatment options in these patients with atrial fibrillation, with high freedom from recurrence after a mean of two ablation procedures.Freedom from recurrence after ablationCharacteristics of left atrium (LA)

Left atrial enlargement: a crucial indicator for identifying atrial fibrillation in patients with hypertension

Abstract Background Left atrial enlargement resulting from hypertension is closely linked to the development and persistence of atrial fibrillation (AF). The newly proposed staging recognizes AF as disease continuum, which makes us aware that AF prevention should focus on the Pre-AF stage, and atrial enlargement is one of the important manifestations in this stage. Previous scoring systems, such as CHA2DS2-VASc and C2HEST, along with the recently highlighted left atrial diameter (LAD), have been significant tools for predicting AF occurrence. However, a comprehensive assessment of their utility is currently lacking. Purpose This study aims to explore the role of left atrial size in identifying atrial fibrillation (AF) among hospitalized hypertensives, and to compare its recognition effectiveness with previous scoring systems. Methods We conducted a cross-sectional analysis within hospitalized hypertensives. The discovery, internal and external validation datasets were established. The XGBoost was employed to identify key variables related to AF occurrence, which were ranked based on their importance scores. To gauge the predictive prowess of LAD regarding AF occurrence, we plotted the receiver operating characteristic curve (ROC) and calculated the area under the curve (AUC). This enabled us to pinpoint the LAD cutoff value corresponding to the maximum Youden index, indicative of susceptibility to AF. Subsequently, Youden index determined the optimal cutoff value from the ROC curve. Delong’s test compared the identification abilities of different tools within the same dataset. Logistic regression analysis assessed the correlation between clinical variables and left atrial size. Results The XGBoost revealed 17 variables affecting AF occurrence in hypertensives, with LAD, age, and HF ranking among the top 3 (Figure 2a). LAD had a more pronounced impact on AF occurrence than other variables. LAD-based identification of AF in hypertensives had AUC of 0.827 (95%CI: 0.816-0.837), with an optimal cutoff of 38mm. Subgrouping the study population by LAD≥38mm, ROC curves showed AUCs of 0.757 (95%CI: 0.745-0.768) for the discovery set, 0.750 (95%CI: 0.731-0.768) for internal validation, and 0.759 (95%CI: 0.743-0.776) for external validation. LAD≥38mm had a more higher and stable AUC value for judging the AF occurrence than CHA2DS2-VASc and C2HEST scores (Figure 2b). Hypertensives with LAD≥38mm had a 9.72-fold higher AF risk than those with LAD<38mm. Conclusion LAD is a pivot determinant for AF occurrence. LAD≥38mm is a valuable identifier for high-risk hypertensives prone to AF.Figure 1.Center illustrationFigure 2.XGboost and Delong’s test of ROC

Orthostatic blood pressure changes and incident atrial fibrillation in patients with hypertension: Insights from the SPRINT trial

Abstract Background Exaggerated orthostatic changes in systolic blood pressure (SBP) were associated with adverse cardiovascular events. However, the predictive role of SBP hyperactivity to standing on incident atrial fibrillation (AF) is unclear. Purpose We aim to assess the association between orthostatic SBP changes and incident AF. Methods We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. Participants with standing SBP <110 mm Hg were not eligible for randomization according to the SPRINT protocol. Participants without AF who had seated and standing SBP measurements at baseline and available baseline or follow-up ECG were included in this analysis. Orthostatic SBP changes were defined as standing SBP minus seated SBP. Patients were grouped into tertiles of orthostatic SBP changes. AF was ascertained from the standard 12-lead ECG obtained at baseline, year 2, year 4, a close-out visit, and any visit when suspected of serious adverse events. We used Cox proportional regression models and restricted spline curves to assess the association of orthostatic SBP changes with incident AF. Results Among 8,455 participants included in this analysis, 327 incident AF cases occurred during follow-up. The restricted spline curve depicted a U-shaped relationship between orthostatic SBP changes and incident AF in the unadjusted model (P for nonlinearity = 0.012) (Figure 1). After adjusting for age, female, race, smoking, alcohol use, history of cardiovascular disease, history of chronic kidney disease, and body mass index, a SBP increase ≥ 6 mm Hg to standing was independently associated with a 43% higher risk of incident AF (HR: 1.43; 95% CI: 1.07-1.90; P = 0.014) compared to nonsignificant orthostatic SBP changes (>-4 mm Hg to <6 mm Hg). A SBP decrease ≥ 4 mm Hg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of >-4 mm Hg to <6 mm Hg (Figure 2). In subgroup analysis, the results presented a similar tendency to the main result. Sensitivity analyses also generated consistent results while additionally adjusting for seated and standing blood pressure or heart rate. Conclusion In this post hoc analysis of the SPRINT trial, exaggerated SBP increase to standing independently predicts incident AF.Figure 1Figure 2

The efficacy of catheter ablation compared to medical therapy in heart failure patients with concomitant atrial fibrillation: A meta-analysis of randomized controlled trials

Abstract Introduction The management of atrial fibrillation in patients with heart failure continues to be a topic of ongoing debate. We conducted a meticulous comparison between two primary treatment modalities: catheter ablation versus medical therapy. Our aim is to assess the efficacy of these interventions in patients presenting with both atrial fibrillation and heart failure, drawing from the randomized controlled trials. Methods A comprehensive literature search was conducted up to February 2024, utilizing databases including PubMed, EMBASE, and Clinicaltrials.gov. A total of 10 randomized studies were identified and their data were extracted and analyzed. The primary outcomes assessed included the impact of catheter ablation on all-cause mortality, cardiovascular death, left ventricular ejection fraction (LVEF %), and 6-minute walk test (6MWT) in meters. Data were analyzed utilizing a random-effects model to calculate weighted mean differences for LVEF and 6MWT, and risk ratios for all-cause mortality and cardiovascular death on Review Manager 5.3 (RevMan 5.3) software. Results In totality, data from 1944 heart failure patients (N = 966 on catheter ablation; N = 978 on medical therapy) with concomitant atrial fibrillation were included. Patients in the catheter ablation group exhibited a significant reduction in all-cause mortality (RR 0.63 [95% CI 0.48, 0.83]; P=0.001; I2 = 17%). Moreover, there was a notable decrease in cardiovascular death among patients undergoing catheter ablation (RR 0.53 [95% CI 0.34, 0.81]; P=0.004; I2 = 20%). Patients who underwent catheter ablation demonstrated a marked improvement in LVEF (MD 5.79 [95% CI 3.13, 8.44]; P <0.0001; I2 = 82%). The 6MWT revealed superior outcomes in the catheter ablation group (MD 22.69 [95% CI 9.87, 35.50]; P=0.0005; I2 = 38%). Conclusion Heart failure patients with concomitant atrial fibrillation undergoing catheter ablation therapy exhibited notable improvements in LVEF and 6MWT, alongside a significantly reduced risk of all-cause mortality and cardiovascular death compared to those receiving solely medical therapy. These findings shed light on the potential advantages and superior outcomes associated with catheter ablation therapy in preserving cardiac chamber function and mitigating mortality in such a patient cohort. However, further investigations are warranted to understand the long-term benefits and optimal management strategies for such individuals.

Identification of the optimal method for measuring left atrium volume as a marker of undetected atrial fibrillation in patients with cryptogenic stroke and high prevalence of overweight

Abstract Introduction Paroxysmal atrial fibrillation (AF) is detected in approximately one-third of patients diagnosed with cryptogenic stroke undergoing prolonged ECG monitoring. Several risk factors for AF have been described, including left atrium (LA) enlargement, LA deformation, age, cardiovascular risk factors, and biomarkers as N-pro-BNP and troponin. Specifically, LA enlargement is a direct marker of atrial cardiopathy, which predisposes to AF. However, the methods to calculate LA enlargement vary. While LA biplane volume indexed to body surface area (BSA) remains the standardized method of choice according to current guidelines, it may underestimate the degree of enlargement in overweight patients. Additionally, overweight produces a systemic inflammatory state which is also associated with AF. Purpose The primary objective of the study was to define the best parameter among LA end systolic volume (LAESV), LAESV indexed to BSA (LAESV/BSA), and LAESV indexed to ideal BSA for identifying patients admitted for cryptogenic stroke with undetected paroxysmal AF. The secondary objective was to assess the accuracy of these parameters in both normal-weight and overweight patients. Methods Consecutive patients over 65 years-old diagnosed with cryptogenic stroke in our tertiary hospital were enrolled. All patients underwent 15-days ambulatory ECG monitoring to screen for undetected paroxysmal AF. Clinical, echocardiographic and laboratory data were prospectively collected. Ideal BSA was calculated using the Devine method. The accuracy of LA volume parameters in classifying patients with undetected paroxysmal AF was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The analysis was stratified for overweight status (BMI < 25 or BMI ≥ 25). Results A total of 66 patients (Mean age 78.4 ± 7.6 years; 48% male) were included. Of them, 39 (59%) had hypertension, 16 (24%) had diabetes and 39 (59%) were overweight. AF was present in 21 (32%) patients. The mean LAESV, LAESV/BSA, LAESV/ideal BSA were 56.2 ± 23.0 ml, 34.2 ± 12.6 ml/m2, and 34.7 ± 14.1 ml/m2, respectively. Figure 1 illustrates the ROC curves for LA volume parameters in the main cohort and stratified by overweight status. Overall, no relevant differences in AUC were observed among LAESV, LAESV/BSA, LAESV/ideal BSA in each scenario. However, BMI significantly altered the discrimination performance of LA volume measures, which resulted optimal in normal-weight patients (AUC from 0.838 to 0.886) and absent in overweight patients (AUC from 0.838 to 0.521 to 0.564). Conclusions LAESV, LAESV/BSA, LAESV/ideal BSA show similar discrimination performance in identifying undetected AF in patients with cryptogenic stroke. However, the presence of overweight considerably impacts on the predictive value of LA volume parameters in this clinical scenario.ROC curves

3D modelling-based left atrium geometry analysis to predict atrial fibrillation in patients with cryptogenic stroke

Abstract Introduction Atrial fibrillation (AF) is a high prevalence condition associated with high morbidity and mortality. Its early diagnosis allows to initiate several prophylactic treatments that have proved to improve its prognosis. 3D modeling techniques allow to design accurate representations of cardiac cavities from diverse source images. Purpose We evaluated the association between new geometrical measurements obtained by 3D echocardiographic models of the left atrium (LA) and the presence of underlying paroxysmal AF in patients with cryptogenic stroke (CS). Methods 3D LA volumes from a sample of consecutive patients aged ≥60 years old and admitted to our Stroke Unit with the diagnosis of CS from April 2019 to November 2020 were analyzed. 15 days ECG monitoring was performed after discharge to detect underlying paroxysmal AF. All 3D echo volumes were analyzed by a 3D modeling open-source application. From this analysis several LA geometry parameters were obtained: sphericity, elongation, flatness, major axis length, minor axis length, maximum 2D diameter (max2Ddiam) and surface-volume ratio (S/V). Functional atrial parameters (3D left atrial ejection fraction, LAEF) were also determined. Results 36 patients were analyzed. Mean age was 78 ± 7 years old. 19% were diabetic, 58% had high blood pressure and 14% of patients had history of ischemic cardiomyopathy. Mean body-mass index was 26. These baseline characteristics were equally distributed between groups. Baseline proBNP was significantly higher in patients developing atrial fibrillation (949 vs 275 pg/mL; p= 0,014.). Maximum 2D diameter (max2Ddiam) and Surface-volume ratio (S/V) were the best predictors of AF (AUC of ROC curves: 0.69; 0.49 – 0.88 and 0.63; 0.42 – 0.84, respectively). An optimal cut-off point of 39 mm was selected for max2Ddiam and of 0.20 for S/V. These values were included in a multivariate model adjusted by baseline proBNP. A Max2Ddiam <39 mm and a S/V ≥0.20 were both significantly associated with the presence of paroxysmal AF (OR 6.96; p= 0.048 and OR 12.22; p = 0.043, respectively). Conclusions New geometrical atrial parameters can be obtained from echo 3D models and might be able to predict AF in patients with CS. Further analysis and larger samples are required to better understand these findings.TableFigure

Machine learning to predict incident atrial fibrillation in patients with acute stroke: FIND-AF STROKE

Abstract Background Atrial fibrillation (AF)-related strokes have a high rate of recurrence, and are associated with substantial morbidity, disability, healthcare expenditure, and mortality.(1-3) Detection of AF promises opportunity to prevent recurrent stroke through conversion of antiplatelet to anticoagulant therapy,(4,5) but use of extended monitoring has cost implications.(6) Thus accurately identifying patients with stroke at high risk for AF is important but previous previous models have been developed in small, unrepresentative cohorts.(7) Purpose To develop and validate a simple novel decision support tool for prediction of incident AF after hospitalisation with stroke through machine learning. Methods We developed the model (FIND-AF STROKE) in UK secondary care and death certificate-linked primary care health record data from individuals aged ≥30 years without known AF hospitalized with a stroke or transient ischaemic attack (Jan 2, 1998 to Feb 28, 2022), randomly divided into training (80%) and testing (20%) datasets. We evaluated logistic regression and random forest models for prediction of 2-year AF risk in the testing dataset with internal bootstrap validation, and compared against the CHA2DS2VASC score. Youden index was used to set a threshold for higher and lower risk. Results Of 35 530 UK individuals (mean age 72.1 (SD 12.7) years, 50.9% women), 1742 (4.8%) had developed incident AF at 2 years. Using feature importance a parsimonious version of the model was created requiring only age, sex, ethnicity (white versus other) and five comorbidities. In the testing dataset prediction performance for the random forest algorithm (area under the receiver operating characteristic (AUROC) 0.710, 95% CI 0.685 – 0.736) was superior to the CHA2DS2VASC score (0.645, 95% CI 0.617-0.672) (Figure 1). The threshold for higher risk using the Youden index was 4.81% which resulted in a negative predictive value of 97.6%, sensitivity 0.712, specificity 0.583. Of the post-stroke patients 44% were labelled at higher risk of AF, who were older, had a higher prevalence of comorbidities, and a 3.3-fold higher incidence of AF post-stroke, than those identified as lower risk (Table 1). Conclusions The machine learning FIND-AF STROKE decision support tool can accurately identify individuals at risk of incident AF after stroke to enable a targeted and cost-effective approach to extended monitoring. Validation within cohorts that have undergone extended monitoring post-stroke will give a more accurate estimation of yield at different risk thresholds.Figure 1

Impact of changes in proteinuria on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study

Abstract Background Diabetes mellitus (DM) is a well-known risk factor for atrial fibrillation (AF). Proteinuria is also considered as an independent predictor for AF. However, there is limited data on whether the changes in proteinuria severity can impact the risk of AF among patients with DM. Purpose We aimed to evaluate the association between changes in proteinuria over time detected using a urine dipstick test and the risk of AF among patients with DM. Methods A total of 1,605,495 patients with DM who underwent two biennial health checkups provided by the National Health Insurance Service (NHIS) between January 2013 and December 2016 were included. All patients had two consecutive urine dipstick tests during the checkups. We divided the study population into four groups based on their glomerular filtration rate (GFR): > 90 ml/min, 60-90 ml/min, < 60 ml/min, and those with end-stage renal disease (ESRD). We evaluated the association between the changes in proteinuria over time detected using a urine dipstick test and the risk of AF and their changes by GFR. Results During a median 4.0-year follow-up, AF occurred in 32,391 persons (5.22 per 1,000 person-years). Among 1,605,495 patients who underwent two consecutive urine dipstick tests, 1,453,116 (90.51%) patients had a negative proteinuria on both tests (negative or trace result on both urine dipstick tests), and 68,979 (4.3%) patients had an aggravated proteinuria (from negative to more than 1+ result on subsequent urine dipstick test). While 48,357 (3.01%) patients had a resolved proteinuria (from positive to negative results on subsequent tests) and 35,043 (2.18%) patients had a persistent proteinuria (positive result on both tests). Those with aggravated or resolved or persistent proteinuria showed an increased risk of AF (HR 1.39, 95% CI 1.33-1.46; HR 1.37, 95% CI 1.30-1.45; HR 1.95, 95% CI 1.85-2.06) compared with most subjects who showed subsequent negative results on proteinuria. This result was consistent within every GFR group. However, the tendency of increment of AF risk by changes in proteinuria was more prominent in lower GFR groups (Table). In subgroup analysis, there was no significant difference between male and female. However, the younger aged (< 65 years) group had a more prominent tendency of increased AF risk by changes in proteinuria. Conclusion Changes in proteinuria showed a significant association with the risk of AF in patients with DM. This tendency was prominent in patients with lower GFR. Therefore, careful monitoring of AF risk based on proteinuria changes could be beneficial for those with DM.

Catheter ablation vs medical management for atrial fibrillation in patients with heart failure: a systematic review and metanalysis

Abstract Background Current guidelines recommend a class IIa recommendation for catheter ablation in Atrial Fibrillation [AFIB]. Traditionally, catheter ablation has been known to be more effective in maintaining sinus rhythm than pharmacological management. However, there is sparse evidence to suggest that this translates to improved clinical outcomes in patients with heart failure. We did a systematic review and meta-analysis of randomized trials to compare the efficacy of ablation vs medical management for AFIB in heart failure. Methods A systematic search was conducted for randomized trials from inception to Jan 2024 for studies comparing the outcomes of catheter ablation vs medical management for AFIB in heart failure. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, heart failure hospitalizations, change in LV ejection fraction (LVEF), AF recurrence rate, 6-minute walk test (6MWT), change in MLHFQ scores and cerebrovascular events. Random-effects models were used to calculate the pooled incidence, mean difference (MD), and risk ratios (RRs) with 95% confidence intervals (CIs). Results A total of 10 RCTs with 2,348 patients were included in this study. Pulmonary vein isolation was the mainstay ablation strategy used. Compared with medical management, Ablation was associated with a significant reduction in all-cause mortality (RR- 0.61; 95% CI, 0.48-0.78; P<0.0001). Ablation was also associated with lower cardiovascular (CV) mortality (RR- 0.52; 95% CI, 0.36-0.75; P<0.0004), heart failure hospitalizations (RR- 0.67; 95% CI, 0.54-0.82; P<0.0001) and AF recurrence rate (RR- 0.43; 95% CI, 0.25-0.75; P<0.003). The study showed an improvement in LVEF (RR - 6.05; 95% CI, 3.35-8.75; P<0.0001), 6MWT (RR- 13.99; 95% CI, 4.18-23.81; P<0.005) and in MLHFQ score (RR -6.98; 95% CI, -12.03 to -1.93; P<0.007. There was a statistically significant difference between the 2 cohorts in the rates of cerebrovascular events (RR- 0.68; 95% CI, 0.35-1.30; P<0.24). Conclusion Randomized trials have shown clear benefits with catheter ablation compared to medical management for AFIB in heart failure. Ablation has demonstrated significantly lower all-cause mortality, reduced CV mortality, HF hospitalizations, AFIB recurrence rate, and improvement in LVEF. Patients who underwent catheter ablation showed improvement in functional outcomes like 6MWT and MLHFQ scores. There was no difference in the incidence of cerebrovascular events compared to medical management. This study adds to the growing evidence in the literature for ablation therapy; however, more trials are needed to identify patients for optimal benefits across the spectrum of heart failure patients.Forest PlotsForest Plots

Long-term efficacy and safety of ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) but data on safety and long-term outcomes after catheter ablation for AF in HCM are scarce. Purpose To investigate safety, long-term efficacy and clinical outcomes following AF ablation in patients with HCM and in matched controls. Methods Patients with HCM (n=76) undergoing a first catheter ablation for AF or atrial flutter between 1999 and 2022 at a University Hospital in Sweden were included (age 64±12 years, 43% female). Diagnosis of HCM was based on the European Society of Cardiology definition (left ventricular wall thickness ≥15 mm or ≥13 mm not solely explained by abnormal loading conditions, and combined with family history, genetic components and/or electrocardiogram abnormalities). Patients with HCM were matched with controls (n=152) based on age, gender, ablation type and intervention-year. Patients were followed for a mean of 5 years and study endpoints included heart failure hospitalization (HFH), stroke and mortality. Cox regression analyses were performed for the association between HCM and the endpoints. Results Among the overall population, 121 (53%) underwent pulmonary vein isolation (PVI), 62 (27%) isthmus ablation and 45 (20%) His-Bundle ablation. Patients with HCM had a shorter mean duration of AF before ablation (48 months vs. 66 months; p=0.047) and more severe symptoms as indicated by a higher EHRA class (EHRA class IV: 30% vs. 10%; p<0.01). Procedural success rate of PVI and isthmus ablation was lower in patients with versus without HCM (88% vs. 97%; p=0.02). Procedure related complications (vascular complications, tamponade) were overall similar in both groups (9% in HCM vs. 5% in controls, p=0.17) except for higher rates of pulmonary oedema in patients with HCM (7% vs 1%, p=0.03). There was a nearly two-fold increase in risk of AF recurrence after PVI or isthmus ablation in patients with HCM compared to controls (OR 1.95; 95% CI 1.06-3.58; p=0.03). During follow-up, patients with HCM had an increased risk of HFH (HR 2.55, 95% CI 1.21-5.36, p=0.01) but not of stroke or mortality (Figure 1). Conclusion AF ablation was overall safe in patients with HCM but less effective. Patients with HCM had an increased risk of the individual endpoint of HFH after AF ablation but not stroke or mortality during long-term follow-up.

Sex-specific prognostic implications of new-onset atrial fibrillation in patients treated with dual chamber pacemakers

Abstract Background Right ventricular pacing induces ventricular dyssynchrony, which over time may result in left ventricular dysfunction, increased left ventricular filling pressures, and ensuing left atrial dilatation, with increased risk of atrial arrhythmias. Atrial fibrillation (AF) prior to device implant is associated with worse prognosis, but the prognostic effects of new-onset AF during pacemaker treatment are less well described. Purpose To describe risk factors, incidence, and prognostic effects of new-onset AF after treatment is initiated with a dual chamber pacemaker. To evaluate mortality and risk of heart failure diagnosis or hospitalisation for heart failure in patients who develop AF, compared to those who do not develop AF. Methods All patients without pre-existing heart failure or atrial fibrillation, who received a dual chamber pacemaker at a large-volume tertiary care center during the period 2005–2020 were included. Data was crossmatched between the national pacemaker registry, the population registry and national disease registries. The primary outcome was 10-year mortality, and the secondary outcome was new-onset heart failure. Results 37127 patients were included in the study, of which 14760 (30%) were female. Median age was 76.4 years [interquartile range, IQR, 68.0–83.1] and the most common indication for pacemaker implant was AV block (57.7%), see Table 1. Overall, 10-year survival was higher for female patients, compared to male patients, p<0.0001 (see Kaplan-Meier curve in Figure 1A). Patients who developed new-onset AF had more comorbidities, were slightly older and a higher percentage were men. During follow-up 3661 (9.9%) developed atrial fibrillation within two years (9.1% of female and 10.3% of male patients, p<0.001), at a median of 291 [88–461] days after implant. In multivariable Cox regression analysis with new-onset AF as time dependent covariable and adjusted for clinically relevant covariables, AF was an independent predictor of higher all-cause mortality (HR 1.43 [1.37–1.49], p<0.0001). Risk factors for new-onset AF included increasing age, male sex, hypertension, malignancy, diabetes, chronic obstructive lung disease, chronic renal disease, and sick sinus syndrome indication (all p<0.01). In separate analyses for men and women, the risk factors and magnitude of odds ratios were the same. Conclusion In patients treated with dual chamber pacemakers due to bradycardia or AV block, development of new-onset AF within two years was associated with a higher 10-year mortality. The risk of developing AF was higher for men, but the negative prognostic effect was more pronounced for women.Figure 1A.-B. K-M survival curves

Rhythm control for atrial fibrillation in patients with end-stage or chronic kidney disease

Abstract Background Although early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF), its use in patients with chronic kidney disease (CKD) remains challenging. Purpose This study aimed to investigate the benefits and risks of ERC in CKD. Methods This population-based cohort study included 5,224 patients with AF (65% male, median age 63 years) with CKD stage III–IV (n=3564) and end-stage renal disease (ESRD, n=1660), who underwent ERC or rate control between 2005 and 2015. The primary outcome consisted of cardiovascular death, ischemic stroke, heart failure-related hospitalization, and acute myocardial infarction. Results During a median follow-up of 3.5 years, ERC, compared to rate control, was associated with a reduced risk of the primary outcome (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74–0.98) without increasing the composite safety outcome in CKD stage III–IV (HR 0.99, 95% CI 0.86–1.13). Among patients with ESRD, the primary outcome did not differ between ERC and rate control (HR 0.97, 95% CI 0.81–1.17) but ERC was associated with an increased risk of composite safety outcome (HR 1.29, 95% CI 1.11–1.50), compared to rate control. However, considering the non-adherence to ERC, its comparative effectiveness on the primary outcome was observed in ESRD (HR 0.81, 95% CI 0.68–0.98). Additionally, ablation procedures did not increase the risk of composite safety outcome (HR 0.63, 95% CI 0.32–1.24). Conclusion ERC demonstrated a modest risk-benefit profile in ESRD compared to CKD stage III–IV. Randomized clinical trials should validate the efficacy of ERC, including ablation procedures, particularly in patients with ESRD.

Impact of changes in left heart geometry on predicting new-onset atrial fibrillation in patients with hypertension

Abstract Background Hypertension-induced left ventricular hypertrophy (LVH) increases end-diastolic LV pressure and contributes to left atrial enlargement (LAE), which are associated with development of atrial fibrillation (AF). However, the impact of LVH and LAE and their regression following antihypertensive therapy on AF incidence remains unclear. Purpose This study aimed to investigate the impact of changes in the LVH and LAE status on the occurrence of new-onset AF (NOAF). Methods This retrospective analysis included patients with sinus rhythm who underwent echocardiography at hypertension diagnosis and after 6–18 months. LVH was defined as LV mass index >115 g/m2 (men) and >95 g/m2 (women), and LAE was defined as LA volume index >42 ml/m2. LVH and LAE regression was defined as the absence of LVH and LAE on follow-up echocardiography, respectively. The occurrence of NOAF was assessed in relation to changes in LVH and LAE status. Results Among the 1,464 patients included in the study, 163 (11.1%) patients developed NOAF during a median follow-up of 63.8 months (interquartile range, 35.9–128.5 months). On average, 12 electrocardiograms per patient were reviewed for AF detection. New-onset LVH (adjusted HR 1.88, 95% CI 1.20–2.94, P=0.006) and LAE (adjusted HR 1.89, 95% CI 1.05–3.40, P=0.034) were significant predictors of NOAF. Conversely, regression of LVH (adjusted HR 0.51, 95% CI 0.280.91, P=0.022) or LAE (adjusted HR: 0.30, 95% CI 0.15–0.63, P=0.001) after antihypertensive therapy was associated with a reduced risk of NOAF. The risk of NOAF was higher in patients with LVH and LAE together (adjusted HR 4.30, 95% CI 2.81–6.56, P<0.001) than in those with either LVH or LAE, or those with neither, as determined by follow-up echocardiography. Conclusion In patients with hypertension and sinus rhythm, regression of LVH and LAE following antihypertensive therapy is associated with a decreased incidence of NOAF, whereas newly developed LVH or LAE is associated with a higher risk of NOAF. The changes in left heart geometry can serve as a predictive marker for NOAF in patients with hypertension.

The incidence of atrial fibrillation in patients with interatrial shunt: is it reduced after surgical or transcatheter closure of the shunt?

Abstract Background Atrial fibrillation (AF) is a prevalent diagnosis among individuals with interatrial shunts, and the prevalence increases with age (1). Since the 1990s, interventionists have introduced transcatheter techniques, to close interatrial shunts, while surgical procedures reserved in cases of technical complexity (2). Despite the potential reduction in AF incidence post interatrial shunt closure, discernible modifications in the cardiac conduction system may persist (3). Notwithstanding, reports indicate an incidence of new-onset AF in approximately 10-25% of patients after interatrial shunt closure, with a pronounced prevalence among elderly (4). This study aims to delineate the incidence of AF subsequent to interatrial shunt, surgical och transcatheter, closure within a national cohort in Sweden. Methods The study includes all patients diagnosed with an interatrial shunt, atrial septal defect and patent foramen ovale, classified using the International Classification of Diseases, 10th edition (ICD-10), as documented in the Swedish National Patient Register, along with data sourced from the Cause of Death Register. Patients with multiple diagnoses of other congenital heart diseases are excluded, and interventions performed between 1997 and 2017 are identified using the NOMESCO surgical classification. Comorbidities such as chronic ischemic heart disease, myocardial infarction, heart failure, hypertension, and diabetes are considered, with the primary endpoint being the incidence of AF post-intervention. Results A total of 3,426 patients with interatrial shunts underwent intervention between 1997 and 2017, with a mean follow-up duration of 6.2 years. Among these, 49% (n=1,725) underwent transcatheter closure, while 41 patients underwent both transcatheter and surgical procedures. The mean age was 36 years, with 9% presenting with heart failure at baseline. Before the intervention, 14% (n=483) had AF, increasing to 22% (n=755) post-intervention. Of those developing AF post-intervention, 16% (n=119) experienced the AF event within 60 days, evenly distributed between transcatheter and surgical procedures. Over 40% of patients with post-intervention AF had an average age of 62. The incidence of AF post-intervention was 1.6 per 100 patient-years (see Figure). Stroke incidence was 3.6 per 100 patient-years and the mortality rate was 7% (n=257) during follow up (see Table). Conclusions Patients with interatrial shunts exhibit a high incidence of AF, which further escalates following closure of the interatrial shunt, not only within the first few days post-intervention, particularly among the elderly population. This can relate to high incidence of ischemic stroke.Figure

Ablation strategy for patients with atrial fibrillation and heart failure - a Danish nationwide cohort study

Abstract Introduction Atrial fibrillation (AF) patients with heart failure (HF) face increased risks of AF recurrence and HF admission. Catheter ablation (CA) is a recognized treatment option. Due to observed atrial remodelling and fibrosis associated with ventricular remodelling in HF patients, it could be suggested that a more comprehensive ablation strategy should be applied for these patients. Purpose To examine the risk of AF recurrence and HF admission by ablation strategy for patients with AF and HF. Method This nationwide cohort study was conducted using real-life data from Danish healthcare registries. All patients above 18 years of age, with a diagnosis of AF and HF that underwent first-time CA from January 1st 2010 to December 31st 2018, were identified and included at the date of ablation. Exposure of interest was ablation strategy - pulmonary vein isolation (PVI) or additional ablation to PVI (PVI plus). PVI plus was defined as either roofline, mitral linear ablation, posterior wall isolation, complex fractionated atrial electrograms or ganglionated plexi ablation. Primary endpoint was HF admission and AF recurrence after a 3-months blanking period. AF recurrence was defined by a composite endpoint of first-reached endpoint of either use of antiarrhythmic drugs, AF admission, electrical cardioversions, or AF re-ablation. The relative rates of recurrent AF and HF admission by ablation strategy (PVI or PVI plus) were examined by Cox proportional models using PVI as reference. The analyses were adjusted for clinically important baseline characteristics including age, sex, AF type (paroxysmal or persistent), diagnosis-to-ablation time, procedural year, body mass index, size of left atrium, as well as co-morbidities such as ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease, hypertension, and diabetes. Results The study cohort consisted of 1,270 patients diagnosed with AF and HF undergoing first-time CA, of which 1,119 (88%) received PVI and 151 (12%) received PVI plus. 80% where males in both groups. Median age was 62 for the PVI group and 64 for the PVI plus group. Severely enlarged left atrium, ischemic heart disease and use of amiodarone were more prevalent in the PVI plus group compared to the PVI group (Table 1). The relative risk of recurrent AF showed a hazard ratio of 1.02 (95% CI: 0.77-1.37) for the PVI plus group compared to the PVI group, and for HF admission the hazard ratio was 0.95 (95% CI: 0.55-1.65) for the PVI plus group compared to the PVI group (Figure 1). Conclusion No significant differences in AF recurrence and HF admission were observed between PVI and PVI plus strategy in AF and HF patients in this observational study. With a diagnosis-to-ablation time exceeding 3 years, it could be argued that advanced atrial remodelling may diminish the impact of reverse atrial remodelling after catheter ablation, irrespective of the ablation strategy employed.Table 1Figure 1

Risk of death, thromboembolic events, and bleeding in elderly patients with Atrial Fibrillation and Clinical Complexity who are not taking oral anticoagulation

Abstract Background Patients with Atrial Fibrillation (AF) often exhibit Clinical Complexity (CC), defined as ≥2 features, i.e. patients aged ≥75 years plus a body mass index (BMI) < 23/kg/m2 and/or bleeding history and/or chronic kidney disease. No data are available about the clinical course of patients with Atrial Fibrillation (AF) and CC who are not taking oral anticoagulation (OAC). Purpose To assess the risk of thrombotic and hemorrhagic events in patients with Atrial Fibrillation (AF) and CC who are not taking OAC. Methods Retrospective study with a health care research network (TriNetX). Based on the ICD-10-CM codes entered between 2011-2022 from 85 health care organizations mainly located in the United States, AF patients ≥75 years with CC were categorized into two groups based on the use of OAC during the last year before the study period. The primary outcomes were the one-year risk of death, major cardiovascular events ([MACE]: heart failure, stroke, and myocardial infarction), and major bleeding (central nervous system, gastrointestinal, internal bleeding, and hypovolemic shock). Secondary outcomes were each component of the primary outcome and catheter ablation. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching 1:1. Results Overall, we identified 271,402 AF CC patients not on OAC (80.1±6.8 years, 46.5% females) and 87,101 AF CC patients on OAC (79.8±6.5 years, 47.6% females). Before PSM, AF CC patients not on OAC showed no significant differences in cardiovascular and bleeding risk factors but were less treated with pharmacological treatment than AF CC patients on OAC. After PSM, no significant differences were found between the two groups, but AF CC not on OAC were at higher risk of all-cause death (HR 1.54, 95%CI 1.50-1.57), MACE (HR 1.13, 95%CI 1.11-1.16), and major bleeding (HR 1.34, 95%CI 1.31-1.38), when compared to AF CC on OAC. AF CC patients not on OAC were associated with a higher risk of each component of the primary outcome and with a lower use of catheter ablation procedures (HR 0.48, 95%CI 0.43-0.54) (Table 1). The risk of the composite outcomes was the highest in those with all the three CC components. A progressive increase in OAC prescription was observed during the follow-up period, with increasing of NOACs and lower use of warfarin being observed. There was a clear temporal relationship between increasing OAC prescription and incidence of bleeding in CC patients (Figure 1) Conclusions AF CC patients not on OAC have a high risk of all-cause death, thrombotic and hemorrhagic events. Over time, increasing NOAC use was associated with more bleeding in CC patients. New antithrombotic approaches aimed at reducing thrombotic risk without increasing bleeding risk are needed in these patients.Figure 1 OAC new prescriptions