Left Atrial Volume Index Research Articles

Left atrial morpho-functional parameters and their correlation with other phenotypic and functional characteristics of hypertrophic cardiomyopathy

Abstract Background Left atrial (LA) volume index (LAVI), LA reservoir strain (LARS) and total atrial conduction time (TACT) (estimated by tissue Doppler imaging) are morphological and functional parameters reflecting LA structural and electrical remodeling, connected to atrial fibrillation development and heart failure progression in various substrates. In hypertrophic cardiomyopathy (HCM), correlation of the above-mentioned parameters with other disease characteristics is not fully investigated. Purpose Aim of this study was to estimate the prevalence of atrial myopathy characteristics such as increased LAVI, impaired LARS and elongated TACT in a cohort of HCM patients without AF history and investigate their correlation with other phenotypic and functional characteristics of the disease such as left ventricular (LV) hypertrophy magnitude, fibrosis extent and diastolic dysfunction grade. Methods We included 100 HCM patients (54±21 years, 75% male, maximum wall thickness 19±3.4mm) without history of atrial fibrillation who have consecutively undergone 2D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). TACT and LARS measurement is shown on left panel. Burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60±7.5%), while 28 (28%) presented outflow tract obstruction and 10 (10%) diastolic dysfunction stage≥2. LGE was observed in 64 patients (64%) occupying 8±5% of left ventricular (LV) mass. Mean TACT was 140±22 msec, with LAVI being 32±16 mL/m2 and LARS 26±14%. Among HCM demographic, phenotypic and functional characteristics tested, age and LV mass index were found to be the only independent regressors of TACT (r=0.54, p<0.0005 and r=0.44, p=0.002 respectively, right upper panel), while E/E’ (r=-0.44, p=0.003) and fibrosis extent (r=0.36, p=0.02) were the strongest predictors of LARS and LAVI values respectively (right lower panel). Conclusions Atrial myopathy parameters seem to correlate with various morphological and functional characteristics of HCM. Atrial electro-mechanical delay assessed through TDI based TACT correlates significantly with LVMI, whereas LARS and LAVI are strong regressors of elasticity properties, partially expressed through diastolic function and underlying fibrosis.

Impact of left atrial appendage closure on left atrial function: insights from the OCEAN-LAAC registry

Abstract Background Percutaneous left atrium appendage closure (LAAC) is an effective therapy to prevent thromboembolic events among patients with atrial fibrillation (AF) (Ref 1). However, since the left atrium appendage (LAA) potentially serves as a part of the left atrium (LA) volume and a buffer for increasing LA pressure, this procedure may impair LA compliance (Ref 2). Purpose In this study, we sought to investigate the effect of LAAC on LA function. Methods/Results The OCEAN-LAAC registry is an ongoing, multicentre Japanese registry including patients who underwent LAAC in Japan (Ref 3). Among 225 patients from the registry, LA volume index (LAVI) and tricuspid regurgitation pressure gradient (TRPG) at baseline and 6 months after the procedure were analysed. In the overall population, no significant increase in LAVI (Abstract Picture 1A) and TRPG (Abstract Picture 1B) was observed (LAVI baseline vs 6 months, 55.0 [44.0, 70.0] ml/m2 vs 55.0 [42.0, 75.6] ml/m2; P = 0.31; TRPG, 25.0 [20.3, 32.0] mmHg vs 25.0 [20.0, 32.0] mmHg; P = 0.85). However, particular patients underwent an increase in LAVI (Abstract Picture 1C), and multivariable analysis showed smaller LAVI and elevated TRPG at baseline, rather than any procedural factors, were significantly associated with an increase in LAVI (Odds ratio (OR) for baseline LAVI: 0.98 [95% confidential interval (CI): 0.97 - 0.996]; OR for baseline TRPG: 1.04 [95% CI: 1.00 - 1.08]). A 5 ml/m2 increase in LAVI at a 6-month follow-up was significantly associated with subsequent heart failure hospitalization (HFH) (Hazard ratio: 3.37 [95% CI: 1.18 - 9.65]) (Abstract Picture 2A). However, this predictive value was not observed in patients with lower LAVI (≤ 55 ml/m2) at baseline; instead, it was observed in those with a baseline LAVI over 55 ml/m² (Abstract Picture 2B). Conclusions In summary, our study did not elucidate the negative impact of LAAC on LA function, yet demonstrated an increase in LAVI at 6 month follow-up was frequently observed in patients with lower LAVI and higher TRPG at baseline. Additionally, increase in LAVI was significantly associated with subsequent HFH, which was more evident in patients with higher LAVI at baseline.

Impact of left atrial size on outcomes in patients with atrial functional mitral regurgitation

Abstract Background Atrial functional mitral regurgitation (AFMR) is caused by mitral annular enlargement following left atrium (LA) enlargement because of atrial fibrillation and/or heart failure with preserved ejection fraction. However, the distribution and clinical impact of LA size are unknown. Purpose To assess the impact of LA volume index (LAVI) on clinical outcomes in patients with AFMR. Methods We investigated patients with ≥moderate AFMR from the REVEAL-AFMR registry. Patients with ≥moderate aortic valve diseases and/or missing LAVI were excluded. The primary endpoint was a composite of cardiovascular death and heart failure hospitalization. Results Of total 871 patients with AFMR (age 78 ± 9 years, men 45%, atrial fibrillation 80%, severe MR 28%), median LAVI was 75 [58-110] mL/m². LAVI <50, 50-99, 100-149, 150-199 and ≥200 mL/m² were present in 117 (13%), 48 (55%), 162 (19%), 61 (7%) and 48 (6%), respectively. In these subgroups, severe MR was present in 10%, 20%, 38%, 61%, and 69% (Figure A), and NYHA III or IV in 8%, 8%, 13%, 13% and 23%, respectively. During the median follow up of 2.9 [2.0-3.2] years, LAVI ≥200 and 150-199 mL/m² were associated with lower event-free survival compared with <50 mL/m² (Figure B) . In the multivariable analysis, LAVI ≥150 mL/m² was an independent risk factor of adverse events (adjusted hazard ratio [HR] 1.69; 95% CI 1.05-2.73, p=0.030), adjusted for age, sex, body mass index, severe symptoms, chronic kidney disease, anemia, severe MR and tricuspid regurgitation (TR). Variables associated with LAVI ≥150 mL/m² were atrial fibrillation (adjusted OR 5.95; 95% CI 1.79-19.8, p<0.01), severe MR (OR 3.99; 95% 2.49-6.39, p<0.01) , elevated PASP (OR 3.10; 95% 1.80-5.33, p<0.01) and TR (OR; 2.46 95% 1.43-4.21, p<0.01), left ventricular end-diastolic volume (adjusted OR 1.26 per 10mL; 95% 1.17-1.36, p<0.01). Conclusion LAVI was 50-99 mL/m² in nearly a half of patients with AFMR, but enlarged to ≥150 mL/m² in 13%. Patients with larger LAVI more frequently had severe symptoms. LAVI ≥150 mL/m² was associated with worse outcomes, independent of MR severity. Severe MR and left ventricular size were strongly associated with LA enlargement other than atrial fibrillation.Figure AFigure B

Serial changes in left atrial strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: insights from VALOR-HCM trial

Abstract Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM phase 3 randomized, double-blind, placebo-controlled clinical trial demonstrated that mavacamten, a cardiac myosin inhibitor, reduces the eligibility for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Mavacamten also resulted in favorable cardiac remodeling, including improvement in left atrial volume index (LAVI), LV diastolic function, and biomarkers (NT-proBNP and troponin T). However, the impact of mavacamten on LA function is not known. Objective We sought to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial. Methods VALOR-HCM included 112 symptomatic obstructive HCM patients (mean age 60 years, 51% male). Patients assigned to mavacamten at baseline (n=56) continued therapy for 56 weeks and those assigned to placebo crossed over to mavacamten (n=52) from week 16-56 (40-week exposure). Echocardiographic LA strain assessment was performed according to the current American and European guideline recommendations, using a vendor-neutral post processing software. For assessment of LA strain components (reservoir, conduit, and contraction), the non-foreshortened apical 4-chamber view was utilized. The zero reference was set at end-diastole. Results Serial changes in LAVI and all components of mean LA strain from baseline to week 56 are shown in the Figure. At baseline, LAVI and all mean LA strain values were worse than reported normal mean thresholds. There was a continued and significant improvement in all 3 LA strain values, from baseline to week 56, along with a significant reduction in LAVI. Improvement in LAVI was seen earlier than improvements in LA strain. There was a significant inverse correlation between change in mean LAVI and LA reservoir strain from baseline to week 56 (r= -0.42, p<0.001). Conclusions In the VALOR-HCM trial, average LAVI and baseline LA strain values were significantly worse than reported normal thresholds. Treatment with mavacamten resulted in an improvement in LAVI and LA strain values from baseline through week 56 suggesting a sustained favorable impact on cardiac remodeling. The advantageous cardiac remodeling associated with long-term treatment with mavacamten may in turn have a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM.Serial changes in LA strain in VALOR-HCM

The impact of pulmonary fibrosis on cardiac function in chronic obstructive pulmonary disease

Abstract Background Emerging evidence indicates the coexistence pulmonary fibrosis and emphysema in patients with Chronic Obstructive Pulmonary Disease (COPD). The effect of pulmonary fibrosis on cardiac structure and function in COPD patients remains unclear. Purpose This study aimed to examine the association between the degree of pulmonary fibrosis identified on Computed Tomographic (CT) imaging and echocardiographic measures of cardiac structure and function in individuals with COPD. Methods The study included 456 individuals with COPD, participating in a large prospective cohort study. Patients with available CT scans and echocardiograms were included. Local histogram-based assessments of lung density were utilized to determine the percentage of fibrosis. Fibrosis was defined based on the CT attenuation within the range of -600 and -250 Hounsfield units. The association between percent fibrosis and measures of cardiac structure and function were investigated by univariable and multivariable linear regression models. Multivariable adjustments included age, sex, body mass index (BMI), and smoking. In addition, restricted cubic splines were generated to visually present the relationship between the percentage of fibrosis and specific echocardiographic parameters. Results The mean age was 71 (± 8 years), 48% were female, and the median BMI was 27 kg/m2 (IQR: 22; 30kg/m2). The mean forced expiratory volume in 1 second as a percentage of the predicted value (FEV1pp) was 47% (±18%). The mean forced vital capacity of predicted value was 71% (± 19%). The median percentage of fibrosis in the cohort was 4.9% (IQR: 3.9; 6.0%). Patients were stratified into tertiles based upon fibrosis percentage. BMI, frequency of diabetes, and FEV1pp were increasingly positively associated with fibrosis. Furthermore, significant trends for echocardiographic measures found that the patients with the most extensive fibrosis were seen to have impaired left ventricular (LV) ejection fraction (LVEF), lower absolute global longitudinal strain (GLS), increased left atrial (LA) volume index (LAVi), and higher LV mass as compared to those with less significant fibrosis. There were no significant differences between tertiles of fibrosis and age or sex. In univariable linear regression, significant inverse associations between the percentage of fibrosis, LVEF, GLS, and tricuspid annular plane systolic excursion (TAPSE) were seen (Table). For LV mass index and LAVi, significant direct associations were found (Table). After adjusting for potential confounding factors, only GLS and LAVi remained associated with pulmonary fibrosis (Figure). Conclusion This study found that GLS and LA volume were significantly associated with the degree of pulmonary fibrosis, even after adjusting for confounding variables. This may suggest that fibrosis is primarily linked with impaired left-sided measures of cardiac structure and function.Linear Regression ModelsCubic Spline Curves

Predictive value of total atrial conduction time for developing cerebrovascular stroke in patients with sinus rhythm and normal left ventricular systolic function, a case-control study

Abstract Background Stroke is the second leading cause of death worldwide. Recently, atrial cardiopathy has become recognized as a substantial risk factor for cerebrovascular stroke. Greater LA size is linked to stroke in AF patients, but few data linking LA size to stroke in population with sinus rhythm. Purpose To investigate the value of total atrial conduction time (TACT) measured non-invasively by assessing PA-TDI duration as a predictor of stroke in patients who initially presented with sinus rhythm and have normal LV systolic function. Methods In our case-control study, we included 156 patients with acute ischemic stroke and 50 control subjects all presented in sinus rhythm and normal LV systolic function. All participants underwent echocardiography. The bi-plane modified Simpson's approach was used to determine the LV-EF. The left atrial (LA) diameter was measured also left atrial volume index (LAVI) was assessed. The PA-TDI interval was used to estimate the TACT. In the apical four-chamber view, the pulsed-wave tissue Doppler sample was positioned on the lateral and septal walls of the LA above the mitral annulus. The time between the onset of the P wave (lead II) and the peak of the A' wave was called the PA-TDI interval. Also, speckle tracking indices of LA strain were measured. Results LA volume index was larger in the stroke group (39.24±4 versus 33.6±2.8, p: 0.01), PA-TDI duration showed statistical highly significant difference between both groups (165.94±21.695 versus 99.4±22.960, p: <0.001). There were significantly impaired LAS parameters in the stroke group (LA reservoir, contraction & conduit strain, 22.7%, -6.6% & -16.1% versus 40%, -12%, and − 27% in the control group with P < 0.000). ROC curve showed the best cutoff point for LA volume index is >42.2 ml/m2 for prediction of stroke with area under the curve (AUC): 0.7, p value is 0.005. ROC curve showed the best cutoff point for PA-TDI is >155.5 ms. with AUC: 0.9, 90% sensitivity, 91% specificity, p value: <0.001. ROC curve showed that LA reservoir strain and LA stiffness can independently predict stroke at cut-off values of 30% & 24.5% respectively, P < 0.001. Multivariate logistic regression analysis showed that hypertension, LA volume index, LA stiffness and PA-TDI duration are independent predictors of stroke (p: < 0.05, < 0.05, < 0.01 and < 0.001 respectively). Conclusions The assessment of electromechanical asynchrony by measuring the PA-TDI duration may help to predict patients at risk for stroke. It is easy to measure without the need for special software like speckle tracking indices. We also advise patients who exceed the cutoff points of LA volume index and PA-TDI duration to receive antithrombotic therapy for better stroke prevention. Also we recommend adding PA-TDI to CHA2DS2-VASC-HSF score to assess stroke risk in patients with sinus rhythm and paroxysmal AF during their sinus rhythm intervals.

Children after kidney transplantation show severe cardiac alterations

Abstract Sudden cardiac death is among the most common causes of death in patients with chronic kidney diseases (CKD) after pediatric kidney transplantation (KTx), but defined diagnostic procedures identifying children at risk are not established. Echocardiographically detectable damage in the context of CKD has been described, but there are few data after KTx in childhood. The aim was to characterize structural and functional cardiac alterations on cardiac MRI (cMRI) and echocardiography in children after KTx and to elucidate the significance of diastolic dysfunction in this special context. 46 KTx recipients (mean age 16.0±3.5 years) and due to missing reference values 46 age- and sex-matched healthy controls were examined with non-contrast cMRI. Native T1 time (nT1), left ventricular mass z-score (LVMIz), ejection fraction (EF), global longitudinal strain (GLS) were measured. KTx recipients underwent comprehensive echocardiography: EF, mitral inflow (E-, A-wave), TDI e', E/e'-ratio, isovolumetric relaxation time (IVRT), pulmonary venous flow (PVFsys, PVFdia), atrial reversal (PVF-AR) and left atrial volume index (LAVI), left ventricular mass z-score (LVMz). Multivariable linear regression analysis (co-variates: age, sex, height) were used to show associations between cMRI and echo parameters. In cMRI KTx recipients had a siginficant higher nT1 than healthy controls (septal: 1198±49ms vs. 1155±23ms, p<0.0001; lateral: 1141±57ms vs. 1109±37ms, p=0.003). In KTx recipients, LVMIz was higher (0.1±1.1g/m2 vs. -0.3±0.7g/m2; p=0.026), GLS was lower than in healthy controls (-19± 2.1% vs. -20.3±2.7%, p=0.01). While based on cMRI 2 patients were diagnosed with left ventricluar hypertrophy (LVH), 11% (n=5) displayed LVH on echo. EF was preserved in all patients. However, in echocardiography, 90% (n=40) of the KTx recipients showed diastolic parameters out of the age-specific normal range (Fig.1) with changes in two or more diastolic parameters in half of the cohort. Associations with septal nT1 on cMRI could be demonstrated for septal E/e´ (ß=8.415, p=0.042), A-wave (ß=1.037, p=0.045), LAVI (ß=3.347, p=0.002) and PVF-AR (ß=2.945, p=0.021); associations with lateral nT1: septal E/e´ (ß=9.590, p=0.045) and LAVI (ß=3.393, p=0.009) (Fig. 2); 7 (15 %) had an elevated nT1 septal, lateral and E/e´ out of the normal range. Young KTx recipients show a high prevalence of diastolic dysfunction with preserved EF. Impaired diastolic function was associated with structural alterations reflecting myocardial fibrosis. Our findings suggest that a large number of children after KTx suffer from heart failure with preserved EF – an entity not yet defined in children but described for adults, in whom it is associated with sudden cardiac death. Further studies are needed to describe the clinical relevance of these findings, which gain explicit importance, as the prognosis of HFpEF in adults is improved by SGLT2i, a treatment option not yet considered in our high-risk patient group.

Prognostic role of exercise stress echocardiography in asymptomatic severe aortic stenosis

Abstract Background Guidelines recognize the role of exercise stress testing in evaluating functional capacity in patients with asymptomatic severe aortic stenosis (AS). The study aimed to identify the prognostic role of exercise stress echocardiography (ESE) in asymptomatic severe AS. Methods We enrolled 153 asymptomatic patients (70±13 years; 88 male, 57%) with severe AS, aortic valve area (AVA) <1.0 cm2, mean aortic gradient ≥ 40 mmHg, ejection fraction (EF) ≥55%. All were referred for ESE in 7 quality-controlled centers from 5 countries. Rest and ESE assessment also included global longitudinal strain (GLS) and left atrial volume index (LAVI). B-lines were assessed by LUS with the 4-site simplified scan of the third intercostal space. A 4-point ESE score was based on 4 parameters (0 for normal, 1 for abnormal), with the following pre-determined cutoffs of abnormality: ∆-maximal aortic gradient (MAG) ≥20 mmHg; GLS at peak ≤ 19%, according to receiver operating characteristics curve analysis, stress B-lines ≥2; stress LAVI ≥ 34 mL/m2. Follow-up was completed in 142/153 patients (92%). Results At rest, AVA was 0.85±0.14 cm2, maximal aortic gradient: 79±14 mmHg, and peak aortic velocity: 4.42 ± 0.41 m/s. Mean EF at rest: 63.4±5.3% During a median follow-up of 1802 days (IQ range 651-2302), 41 events occurred in 39 patients: 15 all-cause deaths, 17 acute HF, 1 stroke, 1 myocardial infarction, and 7 coronary revascularization. Patients experiencing events displayed a greater increase in MAG during peak ESE, more B-lines with exercise, greater degree of LAVI dilation with exercise and slightly lower GLS compared to those without events (Table). Increase in ESE score was associated with a significant rise (p=0.001) in event incidence from score 0 (n=0/13, 0%) to score 1 (n=2/21, 9.5%), score 2 (n=10/42, 23.8%), and ≥3 (n=27/66, 40.9%), see figure. Conclusions In asymptomatic severe AS cases with preserved LV EF, comprehensive ESE provides early marker of potential cardiac decompensation at follow-up. The composite ESE index, including MAG, GLS, LAVI, and B-lines, holds promise as a prognostic predictor.TableFigure

Peak atrial longitudinal strain to replace atrial volume in diastolic function grading: associations with long-term outcomes in a community-based sample with normal left ventricular ejection fraction

Abstract Background Diastolic dysfunction (DD) often precedes symptomatic heart failure and is a predictor of adverse outcomes; thus, accurate assessment and grading are crucial for early interventions. Current guidelines recommend combining multiple echocardiographic parameters, including left atrial volume index (LAVi), for diagnosing DD in patients with normal left ventricular ejection fraction (LVEF). Recently, peak atrial longitudinal strain (PALS) emerged as a more sensitive marker of left atrial function, although its added value in the grading of DD and associated adverse outcomes is scarcely explored. Purpose We aimed to investigate the impact of replacing LAVi with PALS on DD grading by its associations with long-term all-cause mortality in a low-risk, community-based sample. Methods We retrospectively identified 1319 volunteers from a population-based screening program (mean age 53.8±14.9 years, 59.1% female) with LVEF>50%. Subjects underwent echocardiography to measure mitral annular early diastolic velocities (e’), the ratio between mitral inflow early diastolic velocity (E) and e' (E/e'), tricuspid regurgitation peak velocity, LAVi, and PALS by speckle tracking. Diastolic function was initially classified according to the 2016 ASE/EACVI guidelines into normal, indeterminate, and DD groups and then reclassified by replacing LAVi>34 ml/m² with a standard PALS cut-off of <24%. The primary endpoint was all-cause mortality. Results During the median follow-up time of 11 years, 135 (10,2%) subjects met the primary endpoint. According to guideline definitions, 59 subjects were diagnosed with DD, 128 were indeterminate, and 1132 showed normal function. Kaplan-Meier analysis (Figure 1) showed significant differences in mortality between normal versus indeterminate and DD groups (log-rank p<0.001), with a three-fold (HR [95% CI]: 3.363 [1.802 - 6.274], and nearly five-fold increased risk (HR [95% CI]: 4.935 [1.919 - 12.690], respectively. Notably, no significant difference was observed between the outcomes of the indeterminate and DD groups. When subjects were reclassified using PALS instead of LAVi, 35 had DD, 75 were indeterminate, and 1209 had normal function. This classification resulted in different outcomes between groups (Figure 2, log-rank p=0.003). Compared to the normal, the indeterminate group exhibited a two-fold increase in mortality risk (HR: 2.277 [95% CI: 1.038-4.997]), while the DD group had a ten-fold increased risk (HR: 10.180 [95% CI: 2.870-36.130]). DD was associated with a nearly five-fold increase in mortality risk (HR: 4.724 [95% CI: 2.177-10.250]) compared to the indeterminate group. Conclusions In a community-based sample with normal LVEF, replacing LAVi with PALS in diastolic function classification separated groups with significant differences in their long-term all-cause mortality. This adjustment also reduced the size of the indeterminate group and refined its mortality risk.Figure 1Figure 2

Usefulness of left ventricular mechanical dyssynchrony for predicting atrial fibrillation and adverse outcomes following first atrial fibrillation event

Abstract Background Left ventricular mechanical dyssynchrony (LVMD) has shown to predict many cardiovascular outcomes including ventricular arrhythmias. Our hypothesis is that LVMD can reveal early atrial dysfunction. Purpose The aim of this study was to investigate whether LVMD can be used to predict atrial fibrillation (AF) and adverse outcomes following first AF event in individuals from the general population. Methods A total of 3785 individuals (mean age 55±17 years, 57% women) from the general population free of AF, heart failure (HF) and prior stroke had an echocardiographic examination performed including two-dimensional speckle tracking echocardiography. LVMD was calculated as the standard deviation of the regional time-to-peak strain from the three apical views. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or HF after the diagnosis of AF. Results During a median follow-up of 5 years (interquartile range, 4.4-6.2 years), 142 (4%) individuals were diagnosed with AF, and of these 22 (15%) individuals developed HF or stroke. LVMD was a univariable predictor of AF (per 10ms increase: HR 1.03; 95% CI (1.02-1.05), p<0.001, Figure). The association remained significant even after multivariable adjustment for age, sex, body mass index, diabetes, hypertension, heart rate, previous ischaemic heart disease, systolic blood pressure, diastolic blood pressure, smoking, left ventricular ejection fraction, global longitudinal strain, left atrial volume index (LAVI), and E/e’ (per 10ms increase: HR 1.02; 95% CI (1.00-1.04), p=0.042). LVMD also predicted complicated AF, and the association remained significant even after multivariable adjustment (per 10ms increase: HR 1.05; 95% CI (1.01-1.09), p=0.026). Furthermore, LVMD provided incremental prognostic information over the LAVI with regard to predicting AF (Harrell’s C-statistics 0.66 vs. 0.70, p=0.012). Conclusion In a low-risk general population, LVMD provides prognostic information on the risk of AF. Additionally, LVMD can identify individuals with complicated AF defined as occurrence of either stroke or HF following the diagnosis of incident AF. Furthermore, LVMD provides incremental prognostic information over the LAVI in predicting AF.

Adverse prognostic implications of increased left ventricular force in hypertrophic cardiomyopathy

Abstract Background The left ventricular (LV) force, also known as elastance, serves as a load-independent indicator of contractility and can be noninvasively assessed through echocardiography. In hypertrophic cardiomyopathy (HCM), the heightened presence of the active state of myosin heads results in an increased LV force. Purpose To assess the prognostic value of increased LV elastance at rest in patients with HCM. Methods We enrolled 1420 HCM patients (age 50±16 years, 907 males, 64%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 10 quality-controlled labs from 7 countries. TTE assessment included peak left ventricular outflow tract gradient (LVOTG), EF, and LV force (systolic blood pressure + LVOTG/LV end-systolic volume assessed with 2-D, mmHg/mL). All patients were followed up. All-cause death was the outcome measure. Results At a median follow-up of 83 months, 150 deaths occurred (Group 1). At study entry, Group 1 patients had the same ESC-Sudden cardiac death score compared to survivors (Group 2). In Group 1 compared to Group 2, TTE showed higher values of MR severity, E/e’ , left atrial volume index, estimated systolic pulmonary artery pressure, and force (see table). At multivariable Cox analysis, only age (HR =1.08, 95% CI=1.03-1.14, p=0.001) and force > median value of 5.3 mmHg/mL (HR = 2.14, 95% CI 1.53-2.99, p=0.020) were independent predictors of mortality. Ten-year survival was 95% in the pooled first (<3.8 mmHg/mL) and second (3.8-5.2 mmHg/mL) quartiles vs 80% in the pooled third (5.3-7.8 mmHg/mL) and fourth quartiles (>7.8 mmHg/mL), see figure. Conclusion HCM patients with higher values of resting LV elastance show a worse survival, highlighting the dark prognostic side of an excess of force in these patients. Table Legends E/e’, early mitral inflow to early mitral annulus motion ratio, EF, left ventricular ejection fraction, LAVI, left atrial volume index; LVOTG, left ventricular outflow tract peak gradient, MR, mitral regurgitation; MWT, maximal wall thickness, NYHA, New York Heart Association classification, RWT, relative wall thickness; SCD risk, risk score for sudden cardiac death in hypertrophic cardiomyopathy, SPAP, systolic pulmonary arterial pressure.Table.Clinical and TTE findingsFigure.Survival in the force quartiles

Prognostic yield of echocardiographic measures of cardiac structure and function in HFrEF patients with vs without an ICD or CRT-D

Abstract Background Selected echocardiographic measures of cardiac structure and function are known to be associated with mortality in patients with Heart Failure with reduced Left Ventricular (LV) Ejection Fraction (HFrEF). Whether the predictive ability of measures of cardiac structure and function remain after implantation of an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy-Defibrillator (CRT-D) is unknown among patients with HFrEF. Purpose To compare the predictive ability of echocardiographic measures of cardiac structure and function in HFrEF patients with or without an ICD/CRT-D. Methods Echocardiographic examinations were performed between 2003 and 2013 and retrieved from 2168 patients with HFrEF. Patients that had an ICD or CRT-D implanted during follow-up were identified through registries. The endpoint was all-cause mortality and follow-up was 100% to date. Images were analyzed offline in accordance with current guidelines. Associations were assessed by Cox multivariable regression and Cox univariable interaction models. Results After a median of 169 days, 677 patients had an ICD or CRT-D implanted. In total, 68% vs 80% of patients with and without an ICD, respectively, were men (p<0.001) and the median age were 70 vs 71 years (p=0.192). There was a significant difference in resting heart rate (median 74 vs 69, p<0.001) and frequency of ischemic heart disease (64% vs 81%, p<0.001) between the groups. Patients with an ICD had a higher mortality rate (69 per 1000 people/year vs 92 per 1000 people/year, p<0.001) and died significantly faster (median 9.3 vs 8.2 years, p<0.001). Patients with an ICD had higher Left Atrial (LA) End Systolic Volume (59.2 vs 67.3, p<0.001), LA Volume Index (28.5 vs 33.9, p<0.001), LV End Diastolic Volume (137.7 vs 153.7, p<0.001), and LV Mass Index (114.5 vs 124.5, p<0.001), as well as lower LA strain (9.8 vs 6.3, p<0.001) and TAPSE (2.0 vs 1.7, p<0.001). In patients without an ICD, Right Ventricular strain was associated with mortality (HR = 1.05 per 1% decrease mm/m2 [1.005, 1.11] when adjusting for covariates whereas in patients with an ICD, LA Volume Index (HR 1.14 per 1 increase [1.03, 1.25], and LV Ejection Fraction (HR 0.96 per 1% increase [0.92, 0.99]) were associated with mortality when adjusting for covariates. ICD/CRT-D implantation significantly modified the prognostic yield of LV End Diastolic Volume (HR per 1 ml increase: 0.99 without vs 1.01 with an ICD/CRT-D, p=0.005) and LV Mass Index (HR per 1 g/m2 increase: 1.00 without and 1.01 with an ICD/CRT-D, p=0.031). Conclusion Different echocardiographic measures were stronger prognosticators in HFrEF patients with and without an ICD or CRT-D, respectively, and ICD implantation modified the prognostic yield of LV End Diastolic Volume and LV Mass Index in HFrEF patients.Table 1Forest plot

Impact of left atrial stiffness measurement as a pre-procedural predictor of an extensive left atrial low-voltage area

Abstract Background The presence of a left atrial (LA) low-voltage area (LVA) after pulmonary vein isolation for atrial fibrillation (AF) is a strong predictor of recurrence and LVAs are often an additional ablation target. However, predicting the presence of an LVA before the procedure remains challenging. Purpose To assess the LA stiffness index as a preprocedural predictor of an extensive LVA. Methods We prospectively evaluated 74 patients who underwent catheter ablation for AF and high-density bipolar LA voltage mapping during sinus rhythm or high right atrial pacing. "LVA" was defined as an area with bipolar electrograms (<0.5 mV), while "extensive LVA" was defined as the presence of an LVA that covered more than 15% of the LA surface. Echocardiographic measurements, including the LA volume index (LAVi), E/e' ratio, LA reservoir strain (LASr), and LA stiffness index, calculated as the ratio of E/eʹ to LASr, were performed prior to catheter ablation in all patients. Results Overall, 17 patients (23.0%) had an extensive LVA. Patients with extensive LVAs were older (73 ± 7 vs. 66 ± 8 years; P=0.003), predominantly female (59% vs. 23%; P=0.01), and more frequently showed persistent AF (59% vs. 30%; P=0.04) in comparison to patients without extensive LVAs. According to a receiver operating characteristic curve analysis, the LA stiffness index was more accurate than the LAVi or LASr for predicting extensive LVAs (Figure), allowing using a cutoff value ≥0.6 with 73% sensitivity and 91% specificity. A multivariate logistic regression analysis revealed that the LA stiffness index was an independent predictor of an extensive LVA (odds ratio [OR], 44.11; 95% CI 3.83–507.47, P=0.002). Conclusion The LA stiffness index was a robust predictor of the extent of LVAs in AF patients and thus could be useful for the preprocedural selection of candidates for catheter ablation and to determine the most effective ablation strategies.

Relationship between changes in renal function after acute phase of tafamidis administration and left ventricular diastolic function at mid-term follow-up in transthyretin cardiac amyloidosis

Abstract Background A large number of heart failure (HF) patients present with various degrees of renal dysfunction, known as cardio-renal syndrome. Renal impairment in HF patients is also associated with an independent risk factor for morbidity and mortality. Transthyretin (TTR) amyloidosis (ATTR) is characterized by disintegrated liver-derived TTR that accumulates as amyloid fibrils in the myocardium, leading to initially presenting as left ventricular (LV) hypertrophy and LV diastolic dysfunction. Although there is no proven therapy for patients with ATTR cardiomyopathy (ATTR-CM), tafamidis meglumine, a TTR stabilizer, has been associated with favorable outcomes. Although the kidneys are also an important organ where amyloid deposition occurs, the effect of tafamidis on renal function and its relationship to LV diastolic function is unclear. Purpose The purpose of this study was to investigate the relationship between changes in renal function after the acute phase of tafamidis administration and LV diastolic function at mid-term follow-up in patients with ATTR-CM. Methods We studied 56 patients with biopsy-proven ATTR-CM who were treated with tafamidis. All patients underwent blood examinations before and 45.6 ± 23.0 days after the acute phase of tafamidis administration. Echocardiography was performed before and 15.6 ± 9.8 months after the mid-term of tafamidis administration. The primary endpoint was defined as a composite of cardiovascular death or HF hospitalization for 5.0 years. Results Twelve patients had improved renal function as assessed by estimated glomerular filtration rate in the acute phase after tafamidis administration, while 44 patients deteriorated. In the group with improved renal function in the acute phase after tafamidis administration, pulsed-wave Doppler-derived early diastolic velocity from the septal mitral annulus (E’) and left atrial volume index (LAVI) tended to improve at mid-term follow-up compared to the non-improved group. (E’: 0.8 ± 1.7 cm/s vs. 0.2 ± 1.1 cm/s, p=0.127, LAVI: -8.7 ± 12.0 mL/m2 vs. 0.2 ± 16.8 mL/m2, p=0.093). Furthermore, Kaplan-Meier curve indicated that the occurrence of cardiovascular events for patients with improved renal function in the acute phase after tafamidis administration tended to be lower than those without (log-rank P=0.137). Conclusions The improvement of renal function in the acute phase after tafamidis administration was associated with the improvement of LV diastolic function at mid-term follow-up, leading to favorable outcome. Our findings may provide new insights for the management of patients with ATTR-CM.

Clustering of artificial intelligence derived plaque features for risk stratification for future atrial fibrillation development

Abstract Introduction We previously demonstrated that artificial intelligence (AI)-derived coronary artery plaque features are associated with future development of atrial fibrillation (AF) among patients undergoing CCTA(1). Our results suggest that phenotyping a large dataset of plaque features using data science techniques may reveal associations not visible from univariate analysis. Purpose Use data science analysis of AI-CT plaque characteristics to identify subpopulations at higher risk of AF. Methods We applied dimensionality reduction and visual cluster identification to phenotype our population of patients based on their AI-CT plaque features. We used a single center CCTA registry of patients with prior clinically-indicated CCTA (N=2700) from 2017-2020. Cases of new AF were defined by onset of AF on ECG or telemetry after CCTA via EMR search. Patients with AF prior to CCTA, history of mitral valve surgery, or postoperative AF were excluded. Controls were selected 1:1 by nearest neighbor propensity matching (R. v. 4.0.3.) based on age, sex, tobacco use, HTN, HLD, and diabetes. Atherosclerotic plaques were quantitatively analyzed using a commercially available FDA-approved AI coronary analysis software yielding stenosis area and diameter, remodeling index, volume of calcified/non-calcified/low-density plaques, and number of 2 or more high risk plaques. Uniform Manifold Approximation and Projection (UMAP) dimensionality reduction with cosine distance metric was used to reduce the plaque feature space from 80 dimensions (8 AI measurements per each of 10 anatomical vessel segments in all patients) to 2 dimensions on a scatter plot. Two non-contiguous clusters (i.e. plaque phenotypes) were identified based on visual analysis of UMAP feature reduction (Figure 1). Results 94 cases comprised the study cohort (47 cases and 47 controls). Mean age was 67±11 years. 38% were female. Mean CADRADS score was 1.8±1.52 and mean CAC was 325±622. Mean time from CT to AF was 281±300 days. The majority of AF patients (67%) fell into Cluster 1 (N=36), while Cluster 2 (N=58) contained most of the control subjects (75%). Treating Cluster 1 as a predictor of AF, the PPV and specificity of the UMAP reduction was 67% and 75% respectively, with NPV of 60% and sensitivity of 51% (Table 1). Left atrial volume index (LAVI) was significantly different between the 2 clusters, with mean 56.15±12.42 ml/m2 in Cluster 1 and 46.96±16.03 in Cluster 2 (p=0.0046). LAVI was also significantly different between control subjects in Cluster 1 vs 2, mean 54.84±11.6 vs 41.62±7.92 (p<0.001). Conclusions We demonstrated that UMAP-derived clustering of AI-CT plaque characteristics identifies novel phenotypes for future risk of AF among patients undergoing CCTA. Further, control patients in Cluster 1 were found to have a significantly higher LAVI compared to control subjects in Cluster 2, which supports that membership in Cluster 1 may increase risk of future development of AF.

Progression of myocardial fibrosis is the major determinant of heart failure hospitalization in patients undergoing transcatheter aortic valve implantation

Abstract Background Patient who are hospitalized for heart failure (HF) prior to transcatheter aortic valve implantation (TAVI) are associated with poor prognosis. In this study, we aimed to assess whether myocardial fibrosis (MF) in TAVI patients is strongly involved in prior heart failure hospitalization. Methods We performed a retrospective single-center study, including 93 patients who underwent cardiac biopsies before TAVI from December 2022 to December 2023. The extent of MF was assessed on Masson’s trichrome-stained tissue specimens, using a validated software "ImageJ". Results Prior hospitalization had significant association with BNP (HF hospitalization (+): 461.9[130.4-987.7] vs. HF hospitalization (-):125.3[78.2-228.6], p=0.0014) , aortic valve area index (AVAi) (0.43±0.02 vs. 0.51±0.01, p=0.002), left ventricular ejection fraction (LVEF) (54.4±2.8 vs. 67.2±1.6, p=0.0002), E/e’ (23.4±1.9 vs. 19.1±1.0, p=0.045), left atrial volume index (LAVI)(59.0±3.5 vs. 46.1±1.6, p=0.0013), global longitudinal strain (GLS) (13.2±1.0 vs. 15.7±0.5), and percent area of myocardial fibrosis(7.0[4.8-14.2] vs. 3.3[2.2-7.3], p=0.0002) Moreover, percent area of MF was the most reliable indicator (area under the curve: AUC= 0.75, p=0.0009) of prior heart failure hospitalization (figure 1) among HF parameters which include BNP (AUC=0.73, p<0.0001), AVAi (AUC=0.69, p=0.0024), LVEF(AUC=0.68,p=0.0005), E/e’ (AUC=0.63, p=0.051), LAVI (AUC=0.72, p=0.0022), GLS (AUC=0.65, p=0.035). Furthermore, the ROC curve analyses demonstrated that the best thresholds of LVEF and percent area of MF were 64.9% (60.9% sensitivity and 68.1% specificity) and 4.1% (91.7% sensitivity and 56.5% specificity) for heart failure hospitalization, respectively. When patients were divided into 4 groups according to LVEF 65% and percent area of myocardial fibrosis 4%, a stepwise increase in the proportion of heart failure hospitalization was found in the 4 groups (figure 2). Conclusions This study illustrates that extensive myocardial fibrosis was strongly associated with prior heart failure hospitalization in TAVI patients. Patients with advanced myocardial fibrosis due to aortic stenosis may benefit from earlier treatment with TAVI to prevent further progression of myocardial fibrosis.

Long-term efficacy of concomitant surgical ablation for atrial fibrillation with cardiac surgery

Abstract Background Concomitant surgical ablation (SA) is recommended at the time of cardiac surgery in patients with atrial fibrillation (AF) but it is only performed in the minority due to perceived barriers such as increased risk, longer procedure duration and additional technical skills required [1,2]. Furthermore, long-term outcome reporting is limited to only a few high-volume centres. Purpose We sought to report on our centre’s 11-year experience with cardiac surgery and concomitant SA. Methods This was a retrospective observational study on 625 patients with AF who underwent SA in addition to other cardiac surgery at our centre between April 2011 and March 2022. Patients undergoing standalone SA were excluded. Complications were recorded up to 30 days post-procedure. Freedom from atrial tachyarrhythmias (ATA) was determined by electrocardiography, Holter monitoring and pacemaker interrogation at various time points, if available, with or without additional therapies for AF. Results Mean age was 69 +/- 9.9 years and the median duration of AF was 1.2 years (interquartile range 0.4-3.8), persistent in 79% of patients. The median left atrial volume index (LAVI) was 55 ml/m2 (interquartile range 43-71). Concomitant surgery included coronary artery bypass grafting (26%), mitral (68%), aortic (27%), tricuspid (21%) and/or other (5%). Biatrial Cox-Maze IV was performed in 51% of patients and the left atrial appendage was occluded in 74%. Major complications included 30-day mortality (3%), stroke (3%) and pacemaker implantation (4%). Freedom from ATAs was 80% (312/391), 64% (154/240), 53% (76/144) and 44% (33/75) at 1, 3, 5 and 7 years, respectively (Figure 1). Cox regression demonstrated diabetes mellitus, AF duration, persistent AF and LAVI as predictors of 7-year ATA recurrence. Conclusion Concomitant SA for AF has good early and acceptable longer-term rhythm outcomes with no significantly increased complication rate, which should encourage greater uptake of the procedure.

Improvement of left atrial function after ablation in patients with paroxysmal atrial fibrillation is associated with the presence of heart failure with preserved ejection fraction

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) often coexist and left atrial (LA) function was impaired in both AF and HFpEF. However, It remains unclear if HFpEF is linked to LA function improvement in paroxysmal atrial fibrillation (pxAF) patients post-ablation. Purpose To investigate whether the improvement of LA function after ablation in patients with pxAF combined with HFpEF is better than that in patients without HFpEF. Methods 147 patients with pxAF were enrolled and HFpEF was ascertained based on the H2FPEF score. All patients underwent transthoracic echocardiography (TTE) at baseline and 3 months after ablation. Left atrial volume index (LAVI), left atrial ejection fraction (LAEF) and left atrial peak reservoir strain (LA RS) were measured. Improvement of left atrial function is defined as the difference in the above 3 indicators at baseline and 3 months after ablation. The change of the above atrial functional parameters was compared between patients with high-probability of HFpEF [hp-HFpEF] and medium/low-probability of HFpEF [lp-HFpEF]) in univariate and multivariate analysis. Statistical analyses were conducted using independent samples t-tests, Mann-Whitney U tests, and ANCOVA. Results 147 patients were included (30 hp-HFpEF, 117 lp-HFpEF, mean age 62.6 years, 63.3% men, mean BMI 25.54kg/㎡, mean disease course 28.2 months, mean CHA2DS2-VASc score 1.97). In the univariate analysis, the following factors were significantly different between hp-HFpEF and lp-HFpEF, including BMI (26.95±3.71 vs. 25.18±3.00, p=0.007), CHA2DS2-VASc score (3[3-4] vs. 2[1-2], p＜0.001), LA function at baseline including LAVI (41.59±11.38 vs. 32.57[27.68-41.10], p=0.003), LAEF (45.97±10.26 vs. 57.23±9.08, p＜0.001), LA RS (26.43±10.68 vs. 34.43±10.60, p＜0.001), and difference at baseline and 3 months after ablation in LA function including LAVI (4.92±1.08 vs. 3.33±1.18, p＜0.001), LAEF (13.41±9.71 vs. 2.98±9.69, p＜0.001), LA RS (23.61±10.23 vs. 7.29±6.91, p＜0.001), and in left ventricular (LV) TTE indicators including E/e’ (3.10±2.30 vs. -0.32±2.68, p＜0.001), LV ejection fraction (10.5[7.0-16.5] vs. 2.0[-5.0-6.0], p＜0.001), LV global longitudinal strain (14.94±4.27 vs. 5.15[2.63-8.30], p＜0.001) and LV mass (17.79±28.67 vs 1.50[-8.75-17.00], p=0.006). After adjusted for BMI, CHA2DS2-VASc score, LA function at baseline and difference at baseline and 3 months after ablation in LV TTE indicators, the improvement of LA function 3 months after ablation in patients with hp-HFpEF is better than that in patients with lp-HFpEF: LAVI significantly decreased (4.24±0.21 vs. 3.46± 0.09, p＜0.001), LAEF significantly increased (12.90±2.13 vs. 3.09±0.86, p＜0.001) and LA RS significantly increased (21.44±1.81 vs. 8.02±0.76, p＜0.001) in hp-HFpEF compared with lp-HFpEF. Conclusion Patients with pxAF with hp-HFpEF showed better improvement in LA function after ablation than those with Ip-HFpEF.

Prognostic implications and alterations in left atrial deformation following transcatheter aortic valve implantation for severe aortic stenosis

Abstract Background Left atrial reservoir strain (LARS) as a single parameter estimate of left ventricular (LV) diastolic dysfunction (DD), may provide important prognostic insights into patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Purpose To evaluate the prognostic implications of pre- and post TAVI LARS-defined DD (LARS-DD) grade in patients undergoing TAVI for severe AS and its association with new-onset atrial fibrillation. Methods Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS ≥24%), grade 2 (LARS ≥19 to <24%) and grade 3 (LARS <19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements, no history of atrial fibrillation and with clinical/ECG follow-up following the post-TAVI follow-up echocardiogram were evaluated for the occurrence of new-onset atrial fibrillation. Results A total of 601 patients (median age 81 [76-85] years, 53% male) undergoing TAVI for severe AS were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26 to 58) months, a total of 258 (43%) patients died (Figure 1). In a comprehensive multivariable Cox regression model adjusted for age, sex, EuroSCORE II, New York Heart Association class III to IV symptoms, LV ejection fraction, atrial fibrillation, LA volume index and LV stroke volume index, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one grade increase above LARS-DD grade 0/1, 95% CI 1.07 to 1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated (Figure 2). On multivariable Fine and Gray regression analyses adjusting for age and LA volume index, post-TAVI LARS (SDHR 1.14 per 1% <20%, 95% CI 1.05 to 1.23, P=0.0009), rather than pre-TAVI LARS (SDHR 1.00 per 1% <20%, 95% CI 0.91 to 1.11, P=0.93) was associated with the occurrence of new-onset atrial fibrillation. Conclusions Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS and may enhance risk stratification. In addition, post-TAVI LARS, but not pre-TAVI LARS, was closely related to the occurrence of new-onset atrial fibrillation, likely better reflecting intrinsic LA dysfunction.Figure 1:All-Cause MortalityFigure 2:New-Onset Atrial Fibrillation

Left atrial parameters predict incident atrial fibrillation and flutter in patients with heart failure with reduced ejection fraction

Abstract Background Left atrial (LA) function parameters have shown prognostic value in relation to incidence of atrial fibrillation in the general population, but this remains to be investigated in patients with heart failure with reduced ejection fraction (HFrEF). Purpose This study aimed to investigate the relationship between LA function parameters and the risk of incident atrial fibrillation/atrial flutter (AF/AFL) in patients with HFrEF. Methods Subjects free of AF/AFL were retrospectively included from a HF clinic and followed using the Danish National Patient Registry. Cox proportional hazards regression was used to assess the prognostic value of LA function parameters. These included LA ejection fraction (LAEF), peak atrial longitudinal strain (PALS), peak atrial contractile strain (PACS) and LA conduit strain (LACS). In addition, multivariable Cox regression was performed to adjust for demographic and echocardiographic parameters, including LA volume index (LAVi). The LA function parameters that remained significant in adjusted analysis were examined using cubic splines, and cutoff values corresponding to a hazard ratio (HR) equal to 1 were derived from these. Results The total study population consisted of 435 subjects with a left ventricular ejection fraction (LVEF) ≤45% (mean age 65.6±11.7 years, male sex 70.1%) free from AF/AFL at baseline. During a median follow-up of 11.4 years [IQR: 10.8, 14.2], 111 (25.5%) developed AF/AFL. Subjects who met the outcome were generally older (69.0±8.8 years vs. 64.4±12.4, p<0.001), had lower baseline heart rate, and a higher prevalence of moderate or severe valve disease (12.6% vs. 3.1%, p<0.001). They also had higher LV mass index and LV internal diastolic diameter index, but similar LVEF. These subjects had larger LAVi (30 ml/m2 [IQR: 24, 38] vs. 26 ml/m2 [IQR: 20, 32], p<0.001), while LAEF (33±14.8% vs. 39±14.9%, p<0.001), PALS (20.3% [IQR: 16.2, 26.5] vs. 23.2% [IQR: 18.6, 29.6], p=0.001), and PACS (9.7% [IQR: 6.9, 13.5] vs. 12.0% [IQR: 7.8, 16.4], p=0.004) were all significantly lower. LACS was similar between groups. In univariable Cox regression, all LA parameters were significant predictors of the AF/AFL (LAEF: HR 0.98 per 1% increase, 95% CI 0.96-0.99, p=0.0002, PALS: HR 0.96 per 1% increase, 95% CI 0.94–0.98, p=0.0008, PACS: HR 0.95 per 1%, 95% CI 0.93–0.98, p=0.0024, LACS: HR 0.96, 95% per 1% increase CI 0.92–0.998, p=0.039. In adjusted analysis, however, only LAEF (HR 0.98, 95% CI 0.976-0.995, p=0.0087) and PACS (HR 0.96, 95% CI 0.993–0.999, p=0.044) remained significant. Splines were constructed for LAEF and PACS (Figure 1), and a cutoff for increased risk of AF/AFL at 38% for LAEF and 12% for PACS, respectively, were derived (Figure 2). Conclusion LAEF and PACS are associated with risk of incident AF/AFL in patients with HFrEF, independent of clinical and echocardiographic risk factors. Our results suggest an increased risk of AF/AFL at LAEF below 38% and PACS below 12%.Figure 1 SplinesFigure 2 Cumulative incident curves