Atrial Volume Research Articles

Identification and validation of ventricular rhythmic risk subgroups in hypertrophic cardiomyopathy by clustering analysis including left ventricular strain analysis

Abstract Background The excess mortality in hypertrophic cardiomyopathy (HCM) patients is mainly attributed to the occurrence of ventricular arrhythmia (VA).The prediction of VA remains challenging and could be improved. Purpose The study aimed to characterize the VA risk profile in HCM patients through clustering analysis combining conventional parameters with information derived from left ventricular longitudinal strain analysis (LV-LS). Methods 434 HCM patients (65% men, mean age 56 years) were retrospectively included from two referral centers and followed longitudinally (mean duration 6 years). The validation cohort included 177 HCM patients from an other tertiary French center. Mechanical and temporal parameters were automatically extracted from the LV-LS segmental curves of each patient in addition to conventional clinical and imaging data. A total of 287 features were analyzed using a clustering approach (k-means). The first endpoint for VA included suspected SCD, aborted cardiac arrest, appropriate ICD therapy (AIT), sustained ventricular tachycardia (SVT) and non-sustained ventricular tachycardia (NSVT) during follow-up. Results From the derivation cohort, 4 clusters were identified with a higher rhythmic risk for clusters 1 and 4 (VA rates of 26%(28/108), 13%(13/97), 12%(14/120), and 31%(34/109) for cluster 1,2,3 and 4 respectively) (Figure 1). These 4 clusters differed mainly by the LV mechanics. Patients from cluster 4 had a severe and homogeneous decrease of myocardial deformation (global longitudinal strain (GLS) -11%, normal value ≥ -20%) associated with LV and left atrium (LA) remodeling (left atrial volume index (LAVI) 46.6 vs. 41.5 ml/m², p=0.04 and LVEF 59.7 vs. 66.3%, p < 0.001) and impaired exercise capacity (% predicted peak work 58.6 vs. 69.5%; p= 0.025). Patients from cluster 1 showed a marked deformation delay and temporal dispersion on the segmental analysis associated with a moderate decrease of the GLS (-15.3%; p <0.0001 for GLS comparison between clusters). Patients from clusters 2 and 3 had a small GLS decrease (GLS -17.2 and -16.3%, respectively) with a less severe phenotype for cluster 2 and older patients for cluster 3 (mean age 62.1 vs. 54.1 years; p < 0.0001). The clustering analysis in the validation population resulted in the creation of 4 clusters overlapping the derivation cohort with similar characteristics (Figure 2). Clusters 1’ and 4’ had a higher incidence of ventricular arrhythmia with a VA rate of 22%(5/23), 18%(16/88), 0%(0/17), and 20%(10/49) for clusters 1’,2’,3’ and 4’ respectively. Conclusion Machine-learning-based cluster analysis processing LV-LS parameters in HCM patients identified 4 clusters with specific LV-strain patterns and different rhythmic risk levels. In the future, the automatic extraction and analysis of LV strain parameters could help to improve the risk stratification for SCD in HCM patients.Clustering analysisExternal validation

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.

Atrial functional and ventricular functional mitral regurgitation: definitions, epidemiology, and prognostic implications

Abstract Background Severe functional mitral regurgitation (fMR) can be divided into two subgroups: fMR of atrial (AfMR) and fMR of ventricular origin (VfMR). Studies on AfMR are scarce and inconsistent, lacking a uniform definition of AfMR. Hence, little is known about its epidemiology, morphological features, associated risk profiles, and prognostic implications. Purpose The objective of this study was to develop and test a uniform definition of fMR based on the morphological correlate and to describe demographic characteristics, detail entity-specific morphological features and to investigate the associated prognostic impact. Methods 13052 patients with severe fMR and those at risk of severe fMR (comprising mild and moderate fMR)were included. Based on the ratio of left atrial volume (LA) to left ventricular end-diastolic volume (LVEDV), those with severe fMR (n=1163) were divided into AfMR and VfMR. The median of this ratio was used for allocation. Therefore, a LA/LVEDV ratio ≤ 0.56 indicated predominantly ventricular eccentric remodelling, whereas a ratio > 0.56 indicated predominantly atrial remodelling. Results AfMR was more frequently observed in female patients and peak age was a decade later, compared to VfMR. AfMR was the predominant fMR subtype in patients with heart failure with preserved (76%) and mildly reduced ejection fraction (61%), but a significant proportion could be observed even in patients with heart failure with reduced ejection fraction (32%). Severe fMR was associated with excess mortality for both entities: VfMR HR 1.31 [95% CI: 1.14-1.50], p<0.001, with a more pronounced impact in patients with AfMR HR 1.68 [95% CI: 1.47-1.91], p<0.001; AfMR vs. VfMR: HR 1.27 [95% CI: 1.06-1.54], p=0.011. The association between fMR and excess mortality persisted even after multivariate adjustment. In both entities, ischaemic heart disease was common and resulted in a significant increase of mortality (VfMR: HR 1.67 [95% CI: 1.40-1.98], p for interaction<0.001; AfMR: HR 2.10 [95% CI: 1.75-2.52], p for interaction=0.006). Conclusion Based on the entity-specific morphological correlate, severe fMR can be classified into AfMR and VfMR. AfMR occurs across the entire HF spectrum, is more frequently observed in elderly and female patients, and exhibits a worse prognosis than VfMR. The presence of ischaemic heart disease is associated with a near doubling of mortality in both subgroups of severe fMR.Prevalence of fMRKaplan-Meier analysis

Left atrial volume in obesity and hypertension: an innovative "ideal human" index allows for weighing their impact - a non-contrast cardiac CT study

Abstract Left atrial (LA) enlargement is a common and early feature of cardiac involvement in the natural history of obesity and arterial hypertension (AH). Mechanisms involved in this process are cumulative, and partly shared, thus separating and balancing their contributions is challenging. In a proportion of patients referred for coronary artery calcium (CAC) scoring, these clinical entities are present. The LA volume (LAV) is relatively easy to quantify from a CT scan. Measured LAV values can be misleading unless constitutional parameters (height (h) or body size area (BSA), are considered. We introduced a new indexing parameter, consisting of height and the difference between numerical values of height and BSA. In the "ideal human", the difference is zero. Any deviation from this value determines the share of body mass regardless of height. Aim We hypothesize that a novel indexation approach allows for earlier detection of the increased LAV in normotensive and AH patients considering the body mass index. Method We retrospectively analyzed CT data from 2535 patients, 1658 w (64±10 ys), and 876 m (aged 6±11ys), with CAC scoring over the last 15 years The LAV was determined by using commercially available software. The raw and indexed (for h, BSA, and the novel parameter [h+ (h-BSA)]) LAV volumes were compared in patients with normal BMI (<25kg/msg), overweight (25-29.9), and obesity (≥30) who with normal blood pressure or with AH. Results The LAV was larger in high BMI categories than in normal BMI. In non-AH subjects, the LAV increased from an average of 71 ml (normal) to 80 ml (overweight) and 90 ml (obese). In AH, the LAV increase showed a similar trend of averages (77, 88, 94 ml, F=2.59,p<0.01). Indexing LAVs were non-concordant, as shown in Figure. Thus, one can recognize that LAV normalization for the new index has brought the differences most evident and persuasive. In normal BMI, indexation ways did not significantly affect the LAV estimation. Whilst the body weight increased, no difference could be recognized for values indexing for BSA (red). The LAV indexation for height (blue) cannot help diagnose its increase in obesity. The distinguishing strength can be seen while using the [h-(h-BSA)] denominator (green). It indicates that in any scenario, body mass gain plays a greater role in the LAV increase than AH does. Conclusions Body mass is a more important factor that is associated with LAV than AH.. Common methods of LAV indexing, especially referred to as BSA, introduce errors leading to values mimicking normality in non-healthy people and should be forbidden. The proposed indexation way can help overcome the observed discrepancies and support early recognition of the consequences of obesity and hypertension.

Role of 3D-electro-anatomical mapping on procedural characteristics and outcomes in pulsed-field ablation for atrial fibrillation

Abstract Introduction While the utilization of dedicated 3D-electro-anatomical mapping (EAM) systems for catheter ablation of atrial fibrillation (AF) is crucial using radiofrequency, its potential benefits in pulsed-field ablation (PFA) remain uncertain. This is of particular interest, since some PFA ablation systems will soon be available with integrated 3D-EAM capabilities. Objectives To compare the procedural characteristics and outcomes of patients undergoing PFA for pulmonary vein isolation (PVI) with mapping and with no mapping. Methods We prospectively enrolled patients undergoing their first PVI at a tertary referral center. In patients undergoing PVI with mapping, a multipolar mapping catheter was used to create voltage maps during sinus rhythm pre- and post-ablation. In the non-mapping group PVI was confirmed by assessing entrance block via the PFA catheter. The first 30 cases with mapping were excluded to account for a potential learning curve. Results A total of 197 consecutive patients were included (age 65 [interquartile range (IQR) 58 – 72] years; indexed left atrial volume 40 [IQR 35 – 44] mL/m2). Among these, 127 patients (64%) underwent PVI with mapping and 70 patients (36%) with no mapping. The median procedure duration, left atrial dwell time and the fluoroscopic time for the mapping vs the non-mapping group were 55 [IQR 45 – 67] min vs. 28 [IQR 23 – 35] min (p < 0.001), 38 [IQR 30 – 49] min vs. 15 [IQR 11 – 21] min (p < 0.001), 11 [IQR 9 – 14] min vs. 8 [IQR 7 – 11] min (p < 0.001), respectively. In the mapping group in 9% (11/127 patients) at least 1 PV was incompletely isolated and required additional applications. Acute PVI success was 100%. There were two complications in the mapping group (one stroke, one coronary artery air embolism) and none were observed in the non-mapping group. The recurrence rate of atrial arrythmias during a median follow-up of 267 [IQR 164 – 419] days was 14% in the mapping group and 17% in the non-mapping group, p = 0.728. Conclusion In conclusion, the use of PFA with no mapping was associated with a significant decrease in procedural characteristics, while AF-recurrence was not significantly different. The routine use of mapping for PFA-PVI may not be needed.Figure 1

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.

Prognostic implications of right and left atrial strain in diabetes mellitus without coronary artery diseases

Abstract Background 2D- speckle-tracking echocardiography (2D-STE) has recently be used to assess subclinical myocardial dysfunction, however its utility in diabetes mellitus (DM) has been specifically focusing on the longitudinal systolic function of the left ventricle (LV). Aim To assess the prognostic relation between left (LA) and right (RA) systolic and diastolic strain parameters with clinical outcome in patients with DM. Methods Of the initial 1721 diabetic patients screened for this study only 502 consecutive patients with DM were eligible and retrospectively enrolled, and 2D-STE strain parameters assessed on the 2D-TTE images. All patients were prospectively followed for development of new outcome/cardiac events which included hospitalization for acute HF, CVS-related death, new onset AF/AFI, stroke, heart transplantation, or need for ventricular assist device implantation. The 2D-STE analysis was used to measure the peak LA (longitudinal, radial and circumferential) and RA (longitudinal) strain. The long-term outcomes were evaluated for all-cause CVS outcomes and recurrent hospitalization. Results For the 502 eligible patients [mean age:58±4; 58 % male sex], 221 reached the combined endpoint. Mean follow-up was 1.1±0.6years. Both LA and RA strain parameters were significantly impaired compared to normal standard references (p<.0001), the RA was more impaired than LA strain parameters. The best performance parameters predictive of CVS (combined outcomes) events were for LA>RA systolic and diastolic strain, global RA systolic and diastolic strain (AUC: 0.74 and 70) and global LA longitudinal systolic and diastolic strain (AUC: 0.86 and 0.77). The strongest association between the degree of atrial myocardial mechanical dysfunction and risk of cardiovascular events was more evident for LA strain (free wall > global strain) and lesser extend to RA strain. More myocardial mechanical strain impairments were demonstrated in those with higher left atrial volume index (LAVI), NYHA ≥II class, significantly impaired diastolic function, lower strain values (LA, LV, RV), and tricuspid annular plane systolic excursion (TAPSE), p<.001). The LA (free wall) strain impairment was the independent predictors of combined outcome (including survival) after multiple adjustments using different models. Conclusion Patients with DM, LA strain parameters are stronger predictors of outcome than RA and other conventional parameters and should be included for regular clinical screening DM patients as these parameters provide a stronger prognostic stratification.

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

Left ventricular late diastolic strain rate predicts cardiovascular mortality in patients with heart failure with reduced ejection fraction

Abstract Background Left ventricular (LV) strain rate measures provide detailed information regarding LV contraction and filling pressures. These include global systolic strain rate (GSRs), early and late diastolic strain rates (GSRe and GSRa), and ratio of transmitral early filling velocity to GSRe (E/GSRe). Purpose To investigate the prognostic value of strain rate measures with regard to cardiovascular mortality in patients with heart failure with reduced ejection fraction (HFrEF). Methods The study population was retrospectively included from a HF clinic and consisted of patients with LV ejection fraction (LVEF) ≤45%. Echocardiography was obtained within 1 year of referral. The study endpoint was cardiovascular mortality, which was analysed using univariable and adjusted Cox proportional hazards models. Incremental prognostic information was assessed using Harrell’s C-index and continuous net reclassification improvement (NRI). Cubic spline analysis was used to dichotomise variables at a hazard ratio (HR) of 1 for better interpretability. Results The final study population consisted of 1160 patients with HFrEF (mean age 68±11.8 years, 72.7% male, LV ejection fraction (LVEF) 28.6±9.9%). During follow-up (median 10.1 years, IQR: 4.7-13.0), 333 (28.7%) met the outcome. Subjects who met the outcome generally had higher age and prevalence of male sex, a higher burden of comorbidities, and more severely impaired conventional echocardiographic parameters. All four strain rate measures were significantly associated with cardiovascular mortality (GSRs: HR 16.88 95% CI [8.42, 33.84] per 1 s-1 increase, GSRe: HR 0.29 [0.18, 0.47] per 1 s-1 increase, E/GSRe ratio: HR 1.31 [1.22, 1.41] per 1 unit increase, GSRa: HR 0.15 95% CI [0.23, 0.65] per 1 s-1 increase, p<0.0001 for all). However, only GSRa remained an independent predictor in multivariable Cox regression after adjustment for clinical risk factors including sex, age, mean arterial pressure, heart rate, body mass index, cigarette pack years, diabetes mellitus, total cholesterol, ischemic heart disease, and echocardiographic factors including LVEF, global longitudinal strain, tricuspid annular plane systolic excursion, LV mass index, LV internal diameter index, E/e’ ratio and left atrial volume index (HR 0.39 [0.23,0.65], p=0.0003). Furthermore, GSRa provided incremental prognostic information to a model containing all aforementioned parameters (Harrell’s C-index 0.789 vs. 0.792 and continuous NRI 0.158). GSRa was dichotomised at 0.5 s-1, and a Kaplan-Meier curve stratified according to this was plotted (log rank p<0.0001)(Figure 2). Conclusion GSRa is an independent predictor of cardiovascular mortality in patients with HFrEF after multivariable adjustment. GSRa provides incremental prognostic value over conventional echocardiographic measures in risk stratification of HFrEF patients. Our results suggest an increased risk of cardiovascular mortality associated with a GSRa below 0.5 s-1.Figure 1:Spline of HR according to GSRaFigure 2:Kaplan-Meier curve

Screening for stage B heart failure in Type 2 diabetes: natriuretic peptide screening alone misses echocardiographic abnormalities

Abstract Background Heart failure (HF) often manifests as the first cardiac event in individuals with type 2 diabetes mellitus (T2DM). International guidelines recommend natriuretic peptide (NP) screening for stage B/ pre-HF in asymptomatic individuals with T2DM, with echocardiography reserved for those with elevated NPs ("NP-gated" echo approach). Whether this strategy misses individuals with echocardiographic abnormalities despite normal NPs is not fully understood. Purpose To assess the proportion of individuals with T2DM who will be classified as Stage B HF based on biomarker and echocardiography, using independent and combined screening approaches. Methods We utilised the Performance of NT-proBNP In risk Stratification for Cardiovascular Events and mortality in patients with diabetes [PISCES] study (n=765, mean age 62±9 years, 62% men), which enrolled patients with T2DM with no HF. All patients underwent laboratory-based N-terminal pro-B-type NP (NT-proBNP) testing and a point-of-care artificial intelligence echocardiography (Us2.ai). Abnormal echocardiography was defined as left ventricular ejection fraction <50%, left ventricular mass index ≥115(male) or ≥95g/m2(female), left atrial volume index>34 in sinus rhythm or >40mL/m2 in atrial fibrillation, relative wall thickness (RWT) >0.42, E/e' >9, peak tricuspid regurgitation velocity >2.8m/s, pulmonary arterial systolic pressure >35mmHg. Patients with T2DM were classified into either (1) Stage B(biomarker) with elevated NT-proBNP (≥125pg/mL) and normal echocardiography, or (2) Stage B(echo) with abnormal echocardiography and normal NT-proBNP, or (3) Stage B(biomarker+echo) with elevated NT-proBNP and abnormal echocardiography or (4) no abnormalities. Results Among asymptomatic patients with T2DM, the highest proportion of individuals were in Stage B(echo) (43%), followed by those with no abnormalities (37%), Stage B(biomarker+echo) (15%) and Stage B(biomarker) (5%). Patients with Stage B(echo) (vs. no abnormalities) were older (62.5 vs 59.8 years), had a higher prevalence of hypertension (78.4 vs. 72.4%), higher systolic blood pressure (135 vs. 128 mmHg), higher RWT and higher E/e’ (p<0.001 for all). Individuals in Stage B(biomarker+echo) (versus no abnormalities) were older, had a longer duration of T2DM, higher prevalence of hypertension, atrial fibrillation, prior CVD, highest NT-proBNP levels, lowest eGFR levels, and more echocardiography abnormalities (higher RWT and E/e’). Patients identified as Stage B(biomarker) (versus no abnormalities) had a longer duration of T2DM, higher NT-proBNP levels, higher prevalence of comorbidities and comparable echocardiographic measures. Conclusion Among asymptomatic patients with T2DM, a significant proportion have subclinical cardiac abnormalities despite a lack of diagnostic NP elevation. Instead of NP-gated echocardiography, an integrated approach using both NT-proBNP and AI echocardiography may improve the early detection of Stage B HF.

Left atrial volumetric-mechanical coupling index as a marker of subclinical primary heart involvement in systemic sclerosis

Abstract Background Primary heart involvement in systemic sclerosis (SSc) is a common yet often clinically silent marker of poor prognosis. Up to 80% of patients have histopathological evidence of heart involvement, highlighting the need for better screening and diagnostic methods. N-terminal pro-brain natriuretic peptide (NTproBNP), a well-established cardiac biomarker, is often increased in patients with SSc, but with a not fully understood mechanism. Meanwhile, left atrial volumetric-mechanical coupling index (LACI), a new echocardiographic parameter, has been shown to predict cardiovascular outcomes in heart failure patients and the general population, but it has not been studied in SSc. Purpose To identify new echocardiographic parameters, particularly related to left atrial volume and function, as markers of increased NTproBNP in SSc patients without overt heart involvement. Methods Consecutive SSc patients without overt heart disease referred for routine cardiac screening underwent 2D and 3D transthoracic echocardiography, including atrial and ventricular strain analysis. LACI was calculated by both 2D and 3D echocardiography as the ratio between the left atrial volume index and the tissue-Doppler-imaging septal a’ velocity. Patients with significant structural and functional changes suggestive of systolic or diastolic dysfunction or pulmonary hypertension, and those with impaired global left ventricular strain were excluded. Logistic regression, Pearson correlation coefficients, and area under the receiver-operating characteristic curve (AUC) are used to analyze the association and predictive power of LACI for elevated NTproBNP. Results A total of 36 SSc patients (55±10 years old; 34 (94%) women; mean disease duration 14±11 years) were included. Sixteen (44.4%) had diffuse cutaneous involvement (dcSSc). Seventeen (47%) patients had increased NTproBNP levels (i.e. >125 pg/mL). Among all tested variables, 3D LACI had the best correlation with NTproBNP values (r = 0.63, p<0.001). A 3D LACI of >2 associated with NTproBNP of >125 pg/mL (odds ratio 7.33 [95%CI 1.38-38.8]; p=0.01) and predicted these increased values with a sensitivity of 76.9% and a specificity of 81.2% (AUC 0.78). NTproBNP was also correlated with 2D LACI (r=0.55, p<0.001), peak left atrial longitudinal strain (r=-0.42, p=0.01), and left atrial contraction strain (r=0.48, p=0.005). Compared to patients with limited cutaneous involvement, those with dcSSc had higher NTproBNP values (250±139.6 vs 107.2±110.9 pg/mL, p=0.001), higher 3D LACI values (2.6±0.9 vs 1.9±0.5, p=0.02), with similar left atrial and ventricular strain parameters. Conclusion Left atrial volumetric-mechanical coupling index assessed by 3D echocardiography is significantly associated with and predictive of elevated NTproBNP levels in SSc patients without overt heart disease and may be a potentially useful non-invasive marker for screening for early subclinical heart involvement in SSc patients.

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.

AI-enabled automated cardiac chambers volumetry in non-contrast ECG-gated cardiac scans vs. non-contrast non-gated lung scans

Abstract Introduction We have developed an AI-enabled automated volume measurement of cardiac chambers (AutoChamber) that works on ECG-gated coronary artery calcium scans and correlates well with contrast enhanced coronary CT angiography scans. We have recently reported that increased left atrial volume measured by AutoChamber is a strong predictor of new onset atrial fibrillation (AF) in asymptomatic individuals of Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we compare the volumetry results in ECG- gated CAC scans with those of non-gated full-chest lung cancer screening scans in the same individuals. Methods We have studied 169 cases of paired ECG-gated cardiac CT scans and non-gated lung scans obtained from Harbor UCLA. Mean±SD for age was 62.1±10.0 years with 52% female participants. All cases were asymptomatic and were scanned for preventive health assessment. AutoChamber was run on all cases by an independent operator who was not involved in data analysis. P value was calculated using a two-tailed test of significance with α=0.05. Results AutoChamber in cardiac scans vs lung scans reported volume (Mean±SD) for left atrium (LA) was 63.8 ± 18.5 vs. 65.5 ± 19.4, left ventricle (LV) 102.8 ± 25.3 vs. 105.5 ± 25.2, right atrium (RA) 81.9 ± 20.5 vs. 85.7 ± 21.9 right ventricle (RV), 140.7 ± 34.2 vs. 134.2 ± 33.7, left ventricle wall (LVW) 113.0 ± 26.6 vs. 109.7 ± 27.0 respectively (P < 0.0001). Strong correlation was shown between cardiac and lung scans for each cardiac chamber: LA (R = 0.92), LV (R = 0.93), RA (R = 0.91), RV (R = 0.92), and left ventricular wall (LVW) R = 0.95. Conclusions AutoChamber volumetry results are similar in ECG-gated cardiac scans vs non-gated full-chest lung scans. This AI-enabled automated tool is promising as it can provide added value to patients undergoing coronary calcium and lung cancer screening scans flagging enlarged cardiac chambers at risk of AF and heart failure.

Cocoa flavanols alleviate early diastolic dysfunction by decreasing left atrial volume in healthy elderly individuals

Abstract Background Enlargement of the left atrium (LA) predicts future cardiovascular events. Current guidelines recommend cocoa flavanol (CF) intake as it provides cardiovascular and metabolic benefits, although underlying mechanisms are not fully revealed. In this study, we hypothesized that CF intake reverses LA enlargement as a surrogate marker for diastolic dysfunction in elderly individuals without cardiovascular diseases. Methods and Results In a randomized, double-blinded trial, we investigated the effects of CF on systolic and diastolic heart function in healthy elderly individuals. Precise assessment of left-atrial and left-ventricular volume as well as strain rates, all together as emblems of early subclinical cardiac impairment, and markers of systolic function were measured by high-resolution cardiac magnetic resonance (CMR) imaging before and after CF intake. Sixty-three participants (59% male) aged ≥ 55 years received either 500 mg CF (n=30) or a placebo (n=33) twice daily for 30 days. CF counteracted subclinical cardiac dysfunction, evidenced by a reduction in maximal LA volume and LA volume index by 12.6±3.5% (p=0.0063 and p=0.0067) and LV end-diastolic volume (LVEDV) and LVEDV index by ~4.9±1.9% (p=0.049 and p=0.0413). CF intake did not influence strain, strain rate, and systolic function parameters, while the systolic blood pressure decreased by 7 mmHg [~4.7±1.9% (p=0.04)]. Conclusion We provide evidence that CF intake mitigates early changes of diastolic dysfunction and improves cardiovascular health by reversing left atrial and left ventricular remodeling. Cocoa flavanol consumption may prevent age-related cardiac changes in healthy elderly individuals and promote a health span free from cardiovascular diseases.

Cardiac structure and function in patients with chronic obstructive pulmonary disease

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

Impact of dapagliflozin on supraventricular and ventricular arrhythmias, assessed by Holter ECG, in patients with heart failure with reduced ejection fraction

Abstract Background & Introduction Dapagliflozin has significantly reduced morbidity & mortality in patients with heart failure with reduced ejection fraction (HFrEF) (1). Some studies reported supraventricular & ventricular arrhythmia suppression, but Holter ECG was underused, hindering precise assessment of arrhythmia burden. Purpose We aim to assess the impact of dapagliflozin on reduction of arrhythmia in HFrEF at 1 year follow-up (FU) by Holter ECG. Methods This is a single center, prospective study. We have screened 219 HFrEF patients, but only 156 patients were enrolled with LVEF <40% in sinus rhythm from December 2021 to July 2023. All patients had dapagliflozin 10 mg once/day tablet with the standard HF therapy. Clinical evaluation, NYHA evaluation, 6-minute walking test (6MWT), echocardiogram, 24-hours Holter ECG and laboratory work-up were done at baseline, and FU at 6 months and 12 months. Results Males constituted 61.5% of study population; mean± SD participants’ age was 56.8 ± 8.6 years. The most common comorbidities were: ischemic etiology (63.3%), dilated cardiomyopathy (28.1%), hypertension (27.3%), smokers (14.7%), and type II diabetes (31.4%). LVEF was ≤ 35% in 85.9% of patients. We have reported (7.69%) deaths during 1-year FU, and 4 patients (2.56%) didn't complete 1-year FU. Main clinical and echocardiographic findings (baseline vs. 1-year FU): NYHA FC III& ambulant IV dropped from (42.9 to 32.9%), P value<0.05. Distance walked in 6MWT improved from 191.52 ± 75.37 to 219.35 ± 71.51 mean± SD meters, P value<0.05. E/e improved (9.4 to 8.3 cm/s, P value <0.01), LVEF improved (31.3 to 36.4%, P value<0.05). HF emergency: [HF visits dropped (23.7 to 19.2%) and HF hospitalization dropped (11.1 to 7.8%)], P value<0.05. Holter ECG (baseline vs. 1-year FU): Supraventricular Arrhythmia: [Paroxysmal AF reduced (56.2 to 47.6%), frequent PACs (≥ 10%) dropped (3.8 to 1.4%) & Intermittent 1st degree heart block dropped (12.5 to 7.3%)] P value <0.01. Ventricular Arrhythmia: [PVCs >5%-<10% dropped (16% to 9.3%), Frequent PVCs >10% dropped (3.2 to 1.4%), and NSVT dropped (7.8 to 3.1%)], P value <0.01. Stepwise logistic regression multivariable model aiming to predict the occurrence of ventricular and supraventricular arrhythmias has indicated a direct linear correlation with male gender, smoking, body mass index, left atrial volume, and a history of myocardial infarction. Conversely, there is an inverse relationship with systolic blood pressure, 6MWT distance, LVEF, and the administration of dapagliflozin (OR 0.72 [0.61 - 1.07], P value <0.01) concerning the likelihood of supraventricular and ventricular arrhythmias. Conclusions Dapagliflozin has demonstrated significant improvement in functional and echocardiographic parameters in HFrEF patients. Furthermore, it has effectively decreased the incidence of supraventricular and ventricular arrhythmias, identified through 24-hour Holter ECG monitoring during 1-year follow-up.

Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical diabetic cardiomyopathy

Abstract Background Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with so-called diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. Purpose This study aimed to evaluate associations between NT-proBNP concentrations, clinical characteristics, echocardiographic findings, health status and activity, and outcomes from cardiopulmonary exercise testing Methods The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial (ARISE-HF) trial is evaluating the effects of AT-001, a novel aldose-reductase inhibitor in participants with DbCM without a prior history of heart failure (1). Participants were included if they had a known diagnosis of type 2 diabetes and age ≥60 (or ≥45 with a duration of diabetes of ≥10 years or estimated glomerular filtration rate ≤60 mL/min/1.73m2). Participants were required to have evidence of one of: structural cardiac abnormality, elevated cardiac biomarkers, or impaired exercise tolerance, defined as a peak oxygen uptake (VO2) ≤75% of predicted. In this prespecified subgroup analysis of the ARISE-HF trial, 685 participants with baseline echocardiography data, laboratory investigations, and functional assessment were included. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. Results The mean age of participants was 67.4 years and 50% were female. The mean duration of type 2 diabetes was 14.5 years with a mean hemoglobin A1c of 6.98. The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/e’, or right ventricular systolic pressure (Figure 1). In contrast, NT-proBNP was significantly correlated with components of the Kansas City Cardiomyopathy Questionnaire (P<0.001), the Physical Activity Scale in the Elderly (P=0.004), duration of cardiopulmonary exercise testing (P<0.001), peak VO 2 (P<0.001), and ratio of minute ventilation/carbon dioxide production (P=0.002; Figure 2). Conclusion Among highly selected patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals.

Right ventricular-pulmonary artery coupling assessed by two-dimensional strain predicts in- hospital complications in takotsubo syndrome

Abstract Background and purpose Takotsubo syndrome (TTS) may lead to serious in-hospital complications. Our study aims to investigate the prognostic impact of right ventricular-to-pulmonary artery (RV-PA) coupling in patients with TTS. Methods Consecutive TTS patients were prospectively enrolled. RV function was evaluated by RV global longitudinal strain (RVGLS) and RV free wall strain (RVFWS) and RV-PA coupling was measured as the ratio of either tricuspid annular plane systolic excursion (TAPSE), RVGLS or RVFWS to pulmonary artery systolic pressure (PASP). Data about in-hospital complications (defined as acute heart failure, life-threatening arrhythmias and death from any cause) were collected. Results A total of 80 patients were analysed (71±11 years, female 77.5%) and in-hospital complications occurred in 33 (41%). Patients who experienced in-hospital complications had lower LV ejection fraction (LVEF), lower TAPSE/PASP, RVFWS/PASP and RVGLS/PASP and higher left atrial volume indexed (LAVi) values. LVEF (OR 0.913, 95% CI [0.858–0.971], p=0.004) and RVGLS/PASP (OR 0.098, 95% CI [0.012–0.788], p= 0.029) were independent predictors of in-hospital complications. Receiver operating characteristics (ROC) curve analysis showed an area under the curve (AUC) of 0.696 (95% CI [0.57–0.82], p= 0.002) of RVGLS/PASP for the prediction of in-hospital complications. A cut-off value of RVGLS/PASP of ≤ 0.48 %/mmHg showed a sensitivity and specificity of 75% and 60%, and allowed to identify 24% of patients who experienced in-hospital complications despite a preserved LVEF (≥50%). Conclusion RV-PA coupling assessed by RVGLS/PASP may help identifying TTS patients at higher risk of cardiovascular complications with an additional prognostic value to LVEF alone.

Prevalence of stage B heart failure in healthy adults and people with type 2 diabetes

Abstract Introduction People with Type 2 Diabetes (T2D) are at increased risk of heart failure, and as such are classified as having Stage A Heart Failure (SAHF). Those with additional evidence of raised filling pressures, biochemical or structural cardiac changes, without heart failure symptoms, are deemed to have Stage B heart failure (SBHF). Identifying patients with SBHF may help determine those at highest risk of disease progression. Purpose The aim of this work was to assess the prevalence of SBHF in a cohort of asymptomatic healthy volunteers and people with T2D characterised according to current American Heart Association/American College Cardiology/Heart Failure Society of America. Methods A single-centre, prospectively recruited cohort of middle-aged asymptomatic adults with T2D and healthy volunteers, with no history or signs of cardiovascular disease, underwent comprehensive cardiac phenotyping with transthoracic echocardiography and circulating brain natriuretic peptide. Healthy volunteers with risk factors for heart failure, including hypertension and obesity, were excluded from analysis. Prevalence of SBHF was determined by comparing cardiovascular data to proposed standards, left ventricular ejection fraction and global longitudinal strain parameters were omitted from analysis due to data availability. Results We included 383 T2Ds (diabetes duration 9(5,15) years) and 65 healthy volunteers (Table 1); 91% of those with T2D and 65% of healthy volunteers met ≥1 criteria for SBHF (Table 2). Median number of SBHF criteria met in the T2D cohort was 3 (2,4); in particular, a large proportion of the cohort met defined cut offs for relative wall thickness (70.6%), lateral e’ (62.2%), septal e’ (54.1%) and LV wall thickness (47.4%). Of the 65 healthy volunteers, median number of SBHF criteria met was 1 (0,2.5). In healthy volunteers, SBHF was most commonly defined by lateral e’ (40.0%), septal e’ (38.3%), relative wall thickness (32.2%), left atrial volume indexed (22.4%) and serum brain natriuretic peptide (23.3%). Of note, brain natriuretic peptide levels met current SBHF parameters in 18.8% of healthy volunteers and 9.9% people with T2D, which may be attributable to the exclusion of obesity in the healthy volunteer group. Conclusion Using currently proposed standards, a high proportion of middle-aged asymptomatic people with T2D, and healthy volunteers without any risk factors for heart failure, would be categorised as having SBHF. These data strongly suggest that the majority of the proposed parameters for the definition of SBHF are not specific for a UK population and if applied will incorrectly classify many asymptomatic people at high risk of developing heart failure.

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