Left Atrial Functional Parameters Research Articles

Left ventricular, left atrial dysfunction and BNP progression in asymptomatic moderate and severe aortic stenosis

Abstract Introduction and aim Aortic stenosis (AS) is the most common valve disease in industrialized countries. Its prevalence is set to increase considerably in the coming years as the population ages (1). Data regarding the natural evolution in patients with moderate and severe AS are derived from cohorts of patients from 30 years ago (2, 3). We have thought to analyze the evolution of clinical, echocardiographic parameters and blood brain natriuretic peptide (BNP) in a recent cohort of truly asymptomatic patients with moderate to severe AS followed in the Valve Clinic. We also wanted to determine which is the echocardiographic parameter who’s annualized change will influence all-cause mortality in these patients. Methods We have enrolled 63 patients with moderate or severe truly asymptomatic AS (negative exercise test in each patient) followed up in our Valve Clinic from 2010 to 2023 who had at least 2 or 3 transthoracic echocardiographic examination (TTE) of excellent quality while still asymptomatic. All patients had a complete TTE with images suitable for left ventricular (LV) and left atrial (LA) deformation analysis by 2D speckle tracking. All conventional TTE parameters were analyzed as well as BNP measurements at the time of the TTE. Patients were followed up (mean follow up of 401 days) and all-cause mortality was assessed. Results Our results show progression of AS severity, a decrease in LV systolic function (GLS decreased significantly but LVEF and SV index remained changed), progression of LV diastolic dysfunction (progressive increase in E /e' ratio, in LA index volume with a significant decrease in LA reservoir function (PALs)). A progressive increase in estimated systolic pulmonary arterial pressure (PAPs) and a higher probability of pulmonary hypertension during follow-up was observed, while RV function parameters, TAPSE and S’ remained unchanged. BNP levels increased significantly over time. No patient was lost to follow-up and 23 (36.5%) patients died, 3 of cardiovascular cause. After adjustment for sex, age, presence of type 2 diabetes and coronary artery disease, all-cause mortality seemed to be significantly higher in patients with a decrease in LA reservoir function during follow-up (OR 0.77, CI 0.59-0.99, p=0.046). Conclusion To our knowledge, this is the first longitudinal contemporary study to describe the progression of AS and of all parameters of LV, LA, RV function and PHT in moderate to severe truly asymptomatic AS patients followed in a Valve Clinic. A higher risk of all-cause mortality was seen in patients with a poorer LA reservoir function. Annualized changed in LV and LA functional parameters may become a tool to improve risk stratification and therapeutic decision-making in asymptomatic severe AS if larger studies were to confirm our findings.

Left atrial function parameters in patients with a first episode of myocardial infarction: relationship with infarct size and serological inflammatory biomarkers

Abstract Aim Left atrial (LA) function is linked with clinical events in different cardiovascular scenarios. Our aim was to evaluate the associated between LA function and different imaging and serological biomarkers in a cohort of patients with a first episode of acute myocardial infarction (AMI). Methods Prospective cohort of patients with a first episode of AMI treated with percutaneous revascularization in a tertiary care hospital in 2016. All patients underwent echocardiography and cardiac magnetic resonance and blood samples were taken for serological biomarkers analysis. LA function was assessed by means of LA stiffness (E/e’ divided by LA reservoir strain) and LA volumetric-mechanical coupling index [LACI] (LA volume index divided by tissue Doppler a’). Results Mean age of patients in our cohort (n=41) was 57.5±10 years, and 38 (93%) were male. 64% of patients had single vessel coronary artery disease, and median LVEF eas 58% (55-62). Regarding LA function, median LACI was 2.47 (1.99-3.14) and median LA stiffness was 0.27 (0.21-0.44), with 11 (26.8%) patients fulfilling criteria for high LA stiffness. The correlation between these parameters and different imaging and serological biomarkers is shown in Figure 1. There was a significant correlation between LA stiffness and ventricular-arterial coupling, infarct size, and T1 native values. LACI was associated with pulmonary artery systolic pressure, interleukin-6 and soluble CD-14 antigen. Both LA parameters were also significantly associated with left ventricular (LV) ejection fraction and LV global longitudinal strain (Figure 2). Conclusions In our cohort of patients with a first episode of AMI, echocardiographic parameters of LA function were significantly associated with LV function, infarct size and serological biomarkers of inflammation. These parameters might serve as an additional tool for risk stratification in patients with ischemic cardiomyopathy. Figure 1 Figure 2

Effect of SGLT2i on cardiac remodeling in patients with chronic kidney disease undergoing peritoneal dialysis

Abstract Background/Introduction Sodium-glucose Cotransporter-2 inhibitors (SGLT2i) are one of the cornerstone therapies for cardiorenal protection in chronic kidney disease (CKD). However, its use has been restricted in patients with very low glomerular filtration rates (GFR). Therefore, evidence of their use in patients with renal replacement therapy (RRT) is limited. Recent data suggest the positive impact of SGLT2i on cardiac remodeling parameters measured by echocardiogram in patients with heart failure.(1) The use of SGLT2i could be beneficial in patients with CKD undergoing peritoneal dialysis as their cardiovascular risk is high and therapies are limited in such scenarios. Purpose Our aim was to evaluate changes in echocardiographic parameters of cardiac remodeling in patients with CKD and peritoneal dialysis after the use of SGLT2i. Methods Retrospective analysis of a prospective cohort of patients with KDIGO stage 5 CKD receiving peritoneal dialysis. Echocardiographic parameters were measured prior to the introduction of SGLT2i and at a median follow-up of 6.6 months after the initiation of SGLT2i. Results 11 patients were included, mean age was 69.2 years [9.2] , women represented 36.3% of the total and 54.6% of them had a history of congestive heart failure (HF) admission. (Table 1). The mean left ventricular ejection fraction was preserved (54% [9.9]) but subclinical damage was evident by GLS (-13.8% [4.5]). Left Atrial (LA) dilatation and dysfunction were frequent in the basal study, with a mean LA volume index maximum (LAVI max) of 42 ml/m2 [33.1-66.8] and LA reservoir strain of 20.9% [10.6] (Table 2). In the follow-up studies, there was a non-significant trend towards a reduction in LA volume at the expense of LAVI reservoir (-7.1ml/m2; p=0.09). However, there was no improvement regarding LA and LV function parameters. The medication was safe and well tolerated, no new HF admissions occurred during the follow-up. Conclusions Patients with CKD and peritoneal dialysis have echocardiographic signs of atrial enlargement and dysfunction, as well as subclinical LV damage, with reduced GLS. A non-significant trend of LAVI reservoir reduction was observed with the use of SGLT2i and medication was well tolerated. Larger studies are necessary. Table 1. Baseline characteristics Table 2. Echocardiographic parameters

Left atrial stiffness index estimated by echocardiography is an independent predictor of mortality in non-ischemic dilated cardiomyopathy

Abstract Introduction and Objectives Left atrial function parameters have been shown to be important prognostic markers in different clinical settings. Our objective was to evaluate the prognostic role of a non-invasive estimation of left atrial stiffness index using echocardiography in patients with non-ischemic dilated cardiomyopathy (NIDCM). Methods Prospective cohort study of patients with NIDCM evaluated at a tertiary Spanish hospital between 2017 and 2022. Clinical and cardiac imaging variables were collected in a multipurpose registry, and the incidence of clinical events was recorded during follow-up. Left atrial stiffness index was estimated non-invasively as the ratio between E/e' and left atrial strain in the reservoir phase. Results Mean age of patients in our cohort (n=200) was 61 (14) years, and 68 (34%) were women. During a mean follow-up of 3.6 years, 33 (16.5%) patients died, and 54 (27%) were hospitalized for heart failure. Mean left ventricular ejection fraction (LVEF) was 31% (9.5), and mean left atrial stiffness index was 1.3 (0.9), with significant differences between patients with and without events (1.68 (1.1) vs 1.21 (0.8); p=0.005) (Figure). In a logistic regression analysis, the variables significantly associated with all-cause mortality during follow-up were LVEF, E/e' ratio, and left atrial stiffness index (Table). In a multivariable analysis, left atrial stiffness index emerged as an independent predictor of mortality (OR 1.79, 95% CI 1.19-2.69; p=0.005). Conclusions In our cohort of patients with NIDCM, the left atrial stiffness index, which combines information related to filling pressures with left atrial function, was an independent predictor of mortality and could be useful as an additional tool for risk stratification in this setting. Differences in LA stiffness index Logistic regression analysis (mortality)

Evaluation of left atrial function and left ventricular diastolic function during exercise stress echocardiography in patients with different types of atrial fibrillation

Objective: To determine cut-off values for left atrial function parameters at rest and during physical exercise that are specific to patients with atrial fibrillation (AF).Materials and Methods. The prospective single-center study with screening tests of 300 patients was carried out; 297 of them were included in the final analysis. The main cohort of patients was divided into three groups: patients with sinus rhythm without a history of AF, a group with paroxysmal/persistent AF, and patients with permanent AF. Stress echocardiography was performed in all patients according to the ABCDE protocol with additional assessment of left atrial volume index and left atrial strain (reservoir phase) at rest and peak exercise.Results. The left atrial function assessment was successful in 99% (95% CI 98–100%) of patients. The group with sinus rhythm included 240 patients (Group 1), with paroxysmal/persistent AF (PAF) – 38 patients (Group 2), with permanent AF (PermAF) – 19 patients (Group 3). The threshold values of the parameters were determined: left atrial volume and function and LV diastolic function at rest and during exercise, which reliably distinguished the group of patients with sinus rhythm from patients with paroxysmal/persistent AF (Groups 1 and 2, respectively). The best parameters for classifying belonging to the PAF group were the volume and contractility of the LA. Moreover, the quantitative parameter of LA strain classified these groups of patients significantly better during physical exercise (accuracy – 74%, sensitivity – 89%, specificity – 49%) than at rest (accuracy – 64%, sensitivity – 74%, specificity – 51%), with p < 0.004.Conclusions. The obtained threshold values of the left atrial function and volume, as well as E/e' at rest and during physical exercise, provide more accurate differentiation of patients with dyspnea/chest discomfort into groups with and without paroxysmal/persistent AF. The most accurate parameter is the left atrial strain during the exercise stress test.

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

Left atrial function for predicting atrial fibrillation: a machine learning approach

Abstract Background Common risk scores for atrial fibrillation (AF) are based on clinical risk factors, and little is known about the contribution of left atrial (LA) function parameters to risk assessment. Purpose To determine whether a machine learning-based model that includes LA function parameters outperforms a commonly used risk scores, the CHARGE-AF, in predicting AF. Methods Participants in the Atherosclerosis Risk in Communities (ARIC) Study (a community-based cohort study in the USA) who attended visit 5 (2011-2013) and without a history of AF were included in this analysis. Incident AF was ascertained from ECG during study visits, hospitalization discharge codes, and death certificates. Random survival forest methodology was used to build a prediction model for AF; candidate variables included traditional clinical risk factors and measures of LA structure and function. Dataset was randomly split into a training (75%) and testing (25%) cohort. For each variable, importance was measured based on the reduction in Harrell’s c-statistic if the variable was randomly permuted prior to obtaining predicted values. Variables significantly associated with AF were included in the final model. Model calibration was tested using the Greenwood-Nam-D'Agostino (GND) test. Discrimination ability of our model was assessed in the testing cohort using Harrell’s c-statistic and compared with that of the CHARGE-AF model. Results 4,909 participants (59% female, 22% Black, mean age 75 years) were included. During a median follow-up of 7.0 years (1st-3rd quartile: 5.4-7.8), 650 participants developed AF. Variables significantly associated with incident AF were race, triglycerides, systolic blood pressure, coronary heart disease, age, LA maximal volume index, NT-proBNP, and LA reservoir strain (Figure 1). LA reservoir strain was the variable most strongly associated with AF. The final model showed good discrimination (c-statistic (95% CI): 0.734 (0.698-0.768)). The GND test did not detect statistically significant miscalibration (GND p=0.08). Compared with our model, CHARGE-AF had lower discrimination ability (c-statistic (95% CI): 0.635 (0.594-0.677)) and the difference was statistically significant (difference in c-statistic (95% CI): 0.099 (0.043-0.152)). Conclusion A machine learning-based model with few variables including LA function outperforms a commonly used risk model in predicting AF. Incorporation of LA functional assessment may help inform clinicians regarding individual risk of AF.

The predictive value of left atrial functional parameters for recurrence of atrial fibrillation after catheter ablation in patients

Abstract Background Catheter ablation (CA) is a first-line treatment option for patients with symptomatic or drug-refractory atrial fibrillation (AF), yet the recurrence rate of AF post-CA remains considerably high. Studies have reported that left atrial (LA) functional parameters can serve as predictive factors for AF recurrence, however, the results remains controversial. Purpose This study aims to investigate the predictive value of LA functional parameters for AF recurrence following CA in patients. Methods We prospectively enrolled patients with AF who underwent CA for the first time from June 2022 to May 2023 and met the inclusion criteria at our institution. All patients underwent pre-ablation evaluation of LA structure and function, including LA diameter (LAD), LA maximum volume (LAVmax), LA minimum volume (LAVmin), LA pre-systolic volume (LAVpre), LA reservoir strain (LASr), LA strain conduit (LAScd), LA contraction strain (LASct), and LA ejection fraction (LAEF) using three-dimensional speckle tracking echocardiography. AF recurrence was defined as atrial tachycardia occurring 3 months after ablation and lasting longer than 30s. Patients were followed up for 9 months post-CA , and the primary end point was any atrial tachycardia occurring at 3 months after ablation. Results A total of 85 patients with AF were ultimately included in this study, with an average age of 68.9±11.0 years, 54.2% of whom were male. During the 9-month follow-up, 30 patients (35.29%) experienced recurrence postoperatively, while 55 patients (64.71%) still maintained sinus rhythm. Compared with the AF non-recurrence group, the AF recurrence group had significantly increased LAD (46.4±5.5mm vs. 42.3±4.5mm, p<0.05), LAVmax (80.7±21.3mL vs. 67.1±22.0mL, p<0.05), LAVmin (63.8±18.0mL vs. 42.8±16.9mL, p<0.05) and LAVpre (72.4±19.4mL vs. 53.9±16.8mL, p<0.05). Meanwhile, in AF recurrence group, LAEF (21.7±6.8% vs. 37.5±8.0%, p<0.05), LASr (5.1±3.1% vs. 12.0±5.4%, p<0.05), LAScd (-4.0±3.6% vs. -7.3±5.7%, p<0.05), and LASct (-1.0±3.8% vs. -3.3±4.9%, p<0.05) were significantly decreased. Multivariate logistic regression analysis revealed that LASr (OR=0.640, 95%CI 0.425-0.964, p<0.05) and LAEF (OR=0.816, 95%CI 0.694-0.960, p<0.05) were independent risk factors for predicting AF recurrence. ROC curve analysis showed that both LAEF (AUC=0.935, 95%CI 0.871-0.999) and LASr (AUC=0.903, 95%CI 0.833-0.973) possess high predictive values. Furthermore, the combined model of LAEF and LASr (AUC=0.954, 95%CI 0.905-1.000) had a greater predictive value than any one of the two indicators (p<0.05). Conclusion Taken together, these findings indicate that LAEF and LASr are independent predictors of AF recurrence following CA in patients with AF. Combination of the two indicators can more accurately assess the risk of recurrence in AF patients post-CA.

Left atrioventricular coupling index is an independent associate of new-onset AF and stroke in hypertrophic cardiomyopathy: a CMR study

Abstract Background Left atrial (LA) dysfunction is an important marker of disease progression in hypertrophic cardiomyopathy (HCM). LA volumes and functional parameters are associated with new-onset atrial fibrillation (AF) and its complications including stroke. The association between left atrioventricular coupling (LACI), a parameter reflecting the contribution of the left ventricular and LA remodeling to LA dysfunction, with the occurrence of new-onset AF and stroke has not been evaluated. Aim To investigate the association between LACI and the occurrence of new-onset AF or stroke in patients with HCM. Methods In patients with an established diagnosis of HCM and cardiac magnetic resonance (CMR) data, LACI was calculated as the ratio between the LA and the LV end-diastolic volumes. New-onset AF or occurrence of stroke comprised the primary combined endpoint. Cumulative event-free survival rates for the occurrence of the primary endpoint were estimated with the population divided according to a LACI cut-off value of 40%. The association between clinical and CMR variables and the primary endpoint was assessed with univariable and multivariable Cox proportional hazard regression models. Results Of 114 patients with HCM, (mean age 54±16 years, 33 (29%) female, LV ejection fraction 67.0±8.4%), 71 patients (49%) had a LACI > 40% (left atrioventricular uncoupling). During a median follow-up of 4.1 (1.8-6.4) years, 19 (16.7%) patients experienced new-onset AF or stroke. Patients with preserved left atrioventricular coupling (LACI ≤ 40%) had a lower cumulative rate of events compared to those with left atrioventricular uncoupling (log-rank p=0.031, Fig. 1). LACI was independently associated with new-onset AF or stroke after adjusting by the presence of late gadolinium enhancement (LGE) sex and age (HR=23.27, p=0.016). Conclusions In patients with HCM, the presence of left atrioventricular uncoupling is independently associated with the occurrence of new-onset AF or stroke.

Left Atrial Structural and Functional Changes in Adults with Congenital Septal Defects and Paroxysmal Atrial Fibrillation.

Aims. To identify the difference between adult patients with septal defects and paroxysmal atrial fibrillation (AF) and patients without a history of arrhythmia using the left atrial (LA) volume and function parameters, to reveal the parameters associated with AF development. Methods and results. In this prospective study, 81 patients with septal defects and left-to-right shunts were enrolled between 2021 and 2023 and divided into two groups: with paroxysmal AF and without AF. Left atrial function was analyzed based on the indexed left atrial volumes (LAVI and preA-LAVI), ejection fraction (LAEF), expansion index (LAEI), reservoir (LAS-r), conduit (LAS-cd) and contractile (LAS-ct) strain, and stiffness index (LASI) using a Philips CVx3D ultrasound system (Philips, Amsterdam, The Netherlands) and corresponding software. In total, 26 patients with paroxysmal atrial fibrillation (mean age: 59.6 ± 11.7 years, female: 80.8%) and 55 patients with septal defects without any history of arrhythmias (mean age: 44.8 ± 11.6 years, female: 81.8%) were included. All patients were in the NYHA class I or II at baseline. Our findings demonstrated a significant difference between all LA function parameters in the two groups. Upon univariable analysis, the LAVI, preA-LAVI, LASI, LAEF, LAEI, LAS-r, LAS-c, LAS-ct, age, cardiac index, E/A, and RV pressure were found to be associated with AF. The multivariate analysis identified LAVI (OR 1.236, 95% CI 1.022-1.494, p = 0.03), LAS-r (OR 0.723, 95% CI 0.556-0.940, p = 0.02), and LAS-ct (OR 1.518, 95% CI 1.225-1.880, p < 0.001) as independent predictors of AF development. The proposed model demonstrated high sensitivity and specificity with an adjusted classification threshold of 0.38 (AUC: 0.97, 95% CI 0.93-1.00, sensitivity 92% and specificity 92%, p < 0.001). Conclusions. The assessment of LA function using speckle-tracking echocardiography demonstrated significantly different values in the AF group among patients with congenital septal defects. This technique can therefore be implemented in routine clinical management. The key message. Atrial fibrillation development in adult patients with congenital septal defects and a left-to-right shunt is associated with the changes in left atrial function under conditions of an increased preload.

Primary Atriopathy in Mitral Valve Prolapse: Echocardiographic Evidence and Clinical Implications.

Prominent multi-scallop systolic leaflet displacement toward the left atrium (atrialization) is typically observed in bileaflet mitral valve prolapse (MVP) with mitral annular disjunction. We hypothesized that mitral leaflet atrialization is associated with an underlying left atrial (LA) myopathy characterized by progressive structural and functional abnormalities, irrespective of mitral regurgitation (MR) severity. We identified 334 consecutive patients with MVP, no prior atrial fibrillation, and comprehensive clinical and echocardiographic data. LA function was assessed by LA reservoir strain, LA function index, and LA emptying fraction. We also classified the stage of LA remodeling based on LA enlargement and LA reservoir strain (stage 1: no remodeling; stage 2: mild remodeling; stage 3: moderate remodeling; and stage 4: severe remodeling). The primary end point was the composite risk of sudden arrhythmic death, heart failure hospitalization, or the new onset of atrial fibrillation. Bileaflet MVP with no or mild MR had a lower LA reservoir strain (P=0.04) and LA function index (P<0.001) compared with other MVP subtypes. In multivariable linear regression adjusted for cardiovascular risk factors and MR ≥moderate, bileaflet MVP remained significantly associated with lower LA function parameters (all P<0.05). There was a significant increase in the risk of events as the LA reservoir strain and LA remodeling stage increased (P<0.001). In multivariable analysis, stage 4 of LA remodeling remained significantly associated with a higher risk of events compared with stage 1 (hazard ratio, 6.09 [95% CI, 1.69-21.9]; P=0.006). In a large MVP registry, bileaflet involvement is associated with reduced LA function regardless of MR severity, suggesting a primary atriopathy in this MVP subtype. Abnormal LA function, particularly when assessed through a multiparametric approach, is linked to a higher risk of cardiovascular events and may improve risk stratification in MVP, even in those without significant MR.

Left atrial wall thickness measured by a machine learning method predicts AF recurrence after pulmonary vein isolation

Abstract Background Left atrial (LA) remodeling plays a significant role in the progression of atrial fibrillation (AF). Although LA wall thickness (LAWT) has emerged as an indicator of structural remodeling, its impact on AF outcomes remains unclear. We aimed to determine the association between LAWT and AF recurrence after pulmonary vein isolation (PVI). Methods Single-center registry of patients enrolled for radiofrequency PVI from 2016 to 2018. In all cases, a pre-ablation CT scan was performed within less than 48 hours. Mean LAWT was retrospectively determined by a semi-automated machine learning method with minimal human intervention (ADAS 3D®). Additionally, regional tissue thickness was assessed in four locations: roof and inferior, posterior, and anterior walls. In a subgroup of patients, a pre-ablation cardiac magnetic resonance (CMR) was also performed within the same week. LA functional parameters and fibrosis, using 3D delayed gadolinium enhancement, were analyzed. The primary endpoint was AF recurrence after a 3-month blanking period. Results A total of 439 patients (mean age 61±12years, 62% male, 78% with paroxysmal AF) were included. The mean LAWT was 1.4±0.2mm (ranging from 0.9 to 1.9mm). Software processing duration was 8.2±0.4 min, and the mean human input time was 1.3±0.1 min. There was no correlation between LAWT and CT-derived LA-indexed volume (Spearman –0.01, p=0.845). During a median follow-up of 5.8 (IQR 4.9–6.6) years, 238 patients (54%) had an AF relapse. LAWT was an independent predictor of recurrence, after adjusting for known confounders including age, non-paroxysmal AF, LA-indexed volume, and chronic kidney disease (adjusted HR 6.49 [95% CI 2.70-15.49], p&amp;lt;0.001). AF recurrence rates were 11%, 15%, and 21%/year across terciles of increasing LAWT (log-rank p&amp;lt;0.001) – Figure. The posterior LAWT revealed the strongest association with the study endpoint (HR 1.93 [95% CI 1.24-3.02], p=0.004). In the cohort of 62 patients with both CT and CMR, LAWT showed weak correlations with LA ejection fraction and LA coupling index (Spearman &amp;lt;0.25; p=0.054 and p=0.093, respectively), and a moderate correlation with LA fibrosis (Spearman 0.468; p&amp;lt;0.001). Conclusions Mean LAWT, easily assessed by commercially available machine learning software, is an independent predictor of AF recurrence after PVI in the long-term follow-up. This association is mainly driven by the posterior LAWT. Whether patients with increased LAWT should receive tailored therapy deserves further investigation.Figure

“Interstitial fibrosis is associated with left atrial remodeling and adverse clinical outcomes in selected low-risk patients with hypertrophic cardiomyopathy”

Cardiovascular magnetic resonance (CMR) extracellular volume (ECV) allows non-invasive detection of myocardial interstitial fibrosis, which may be related to diastolic dysfunction and left atrial (LA) remodeling in hypertrophic cardiomyopathy (HCM). While the prognostic role of LGE is well-established, interstitial fibrosis and LA dysfunction are emerging novel markers in HCM. This study aimed to explore the interaction between interstitial fibrosis by ECV, LA morpho-functional parameters and adverse clinical outcomes in selected low-risk patients with HCM. 115 HCM patients and 61 matched controls underwent CMR to identify: i) interstitial fibrosis by ECV in hypertrophied left ventricular LGE-negative remote myocardium (r-ECV); ii) LA indexed maximum (LAVi max) and minimum (LAVi min) volumes, ejection fraction (LA-EF) and strain (reservoir εs, conduit εe and booster εa), by CMR feature-tracking. 2D-echocardiographic assessment of diastolic function was also performed within 6months from CMR. A composite endpoint including worsening NYHA class, heart failure hospitalization, atrial fibrillation and all-cause death was evaluated at 2.3years follow-up. HCM patients were divided into two groups, according to r-ECV values of controls. Patients with r-ECV ≥29% (n=45) showed larger LA volumes (LAVimax 63 vs. 54ml/m2, p<0.001; LAVimin 43 vs. 28ml/m2, p〈0001), worse LA function (εs 16 vs. 28%, εe 8 vs. 15%, εa 8 vs. 14%, LA-EF 33 vs. 49%, all p<0.001) and elevated Nt-proBNP (1115 vs. 382pg/ml, p=0.002). LA functional parameters inversely correlated with r-ECV (εs r=-0.54; LA-EF r=-0.46; all p<0.001) and E/e' (εs r=-0.52, LA-EF r=-0.46; all p<0.006). r-ECV ≥29% and LAVi min >30ml/m2 have been identified as possible independent factors associated with the endpoint. In HCM diffuse interstitial fibrosis detected by increased r-ECV is associated with LA remodeling and emerged as a potential independent predictor of adverse clinical outcomes, on top of the well-known prognostic impact of LGE.

Predicting reduced left atrial appendage velocity from echocardiographic left atrial function parameters in patients with atrial fibrillation undergoing catheter ablation

Decreased left atrial appendage velocity (LAAV) is considered a significant risk factor thrombus formation in the left atrial appendage (LAA). The aim of this study was to assess the role of echocardiographic left atrial (LA) function parameters in predicting LAAV in patients with persistent atrial fibrillation (AF) undergoing catheter ablation. We prospectively enrolled consecutive patients with persistent AF undergoing transesophageal echocardiography (TEE) directly before the first AF ablation in 2019–2022. Of the 150 patients enrolled in the study, 29.3% (n = 44) had reduced LAAV values defined as < 25 cm/s. Patients with decreased LAAV values exhibited significantly reduced left atrial reservoir and conduit strain (LASr and LAScd), LA emptying fraction, and average e′ values. This group also presented with a high LA stiffness index (LASI), high LA and right atrial area, and high LA volume index (LAVI) and E/e′ ratio. In multivariable logistic regression analysis, LASI and LAVI remained significant predictors of the reduced LAAV. The threshold values were 1.6 for LASI and 44.47 ml/m2 for LAVI, with area under the curve values of 0.809 and 0.755, respectively. Among all noninvasive echocardiographic parameters, LASI and LAVI were found to be the best predictors of reduced LAAV, with good sensitivity and specificity. Moreover, LASI was found to be the only significant predictor of reduced LAAV defined as < 20 cm/s as well as < 25 cm/s.

Atrial Pacing Negatively Affects Left Atrial Morphological and Functional Parameters Similarly to Atrioventricular Dyssynchrony.

Background and Objectives: Atrioventricular (AV) dyssynchrony as well as atrial and ventricular pacing affect left atrial (LA) function. We conducted a study evaluating the effect of atrial and ventricular pacing on LA morphological and functional changes after dual-chamber pacemaker implantation. Materials and Methods: The study prospectively enrolled 121 subjects who had a dual-chamber pacemaker implanted due to sinus node disease (SND) or atrioventricular block (AVB). Subjects were divided into three groups based on indication and pacemaker programming: (1) SND DDDR 60; (2) AVB DDD 60 and (3) AVB DDD 40. Subjects were invited to one- and three-month follow-up visits. Three subsets based on pacing burden were analyzed: (1) high atrial (A) low ventricular (V); (2) high A, high V and (3) low A, high V. LA function was assessed from volumetric parameters and measured strains from echocardiography. Results: The high A, low V group consisted of 38 subjects; while high A, high V had 26 and low A, high V had 23. A significant decrease in reservoir and contractile LA strain parameters were only observed in the high A, low V pacing group after three months (reservoir 25.9 ± 10.3% vs. 21.1 ± 9.9%, p = 0.003, contractile -14.0 ± 9.0% vs. -11.1 ± 7.8, p = 0.018). While the re-established atrioventricular synchrony in the low A, high V group maintained reservoir LA strain at the baseline level after three months (21.4 ± 10.4% vs. 22.5 ± 10.4%, p = 0.975); in the high A, high V group, a further trend to decrease was noted (20.3 ± 8.9% vs. 18.7 ± 8.3%, p = 0.231). Conclusions: High atrial pacing burden independently of atrioventricular dyssynchrony and ventricular pacing impairs LA functional and morphological parameters. Changes appear soon after pacemaker implantation and are maintained.

Lower left atrial function in young individuals with type 1 diabetes mellitus compared to healthy controls: an echocardiographic study

In adulthood, individuals with type 1 diabetes mellitus may develop a condition of heart failure with preserved ejection fraction. However, subclinical changes to the heart in diabetes are likely to occur prior to the clinical presentation. This cross-sectional study aimed to compare left atrial function by echocardiography between 43 individuals with type 1 diabetes and 43 healthy controls, aged 10–30 years. All participants underwent echocardiography and 2D speckle tracking measurements for left atrial phase function parameters. Physical capacity was assessed by exercise test on a bicycle. Results showed that participants with type 1 diabetes had significantly lower left atrial function parameters than healthy controls (p < 0.05). There was a significant negative correlation between HbA1c means and reservoir and conduit strain (p < 0.05) and individuals with BMI < 30 showed a lower left atrial stiffness (p < 0.05). Individuals with type 1 diabetes and a higher physical capacity did not differ from their healthy peers. Results indicate that lower HbA1c levels, BMI < 30 and a higher physical capacity are favourable in terms of left atrial function in children and young adults with type 1 diabetes mellitus. Left atrial strain by echocardiography might become a new important tool in assessing heart function in T1DM.

Spironolactone improves left atrial function and atrioventricular coupling in patients with resistant hypertension.

To determine the blood pressure independent effects of spironolactone on left atrial (LA) size and function in patients with resistant hypertension (RHTN). Patients with RHTN (n = 36, mean age 55 ± 7) were prospectively recruited. Spironolactone was initiated at 25mg/day and increased to 50mg/day after 4 weeks. Other antihypertensives were withdrawn to maintain constant blood pressure. Cardiac magnetic resonance imaging was performed at baseline and after 6 months of spironolactone treatment and changes in LA functional metrics were assessed. LA size and function parameters were improved (p < 0.05) from baseline to month-6: LA volumes indexed to body surface area (LAVI) were reduced (LAVImaximum 41.4±12 vs. 33.2±9.7 mL/m2; LAVIpre-A 32.6±9.8 vs. 25.6±8.1 mL/m2; median LAVIminimum 18.5 [13.9-24.8] vs. 14.1 [10.9-19.2] mL/m2); left atrioventricular coupling index was reduced (28.2±11.5 vs. 22.7±9.2%); LA emptying fractions (LAEF) were increased (median total LAEF 52.4 [48.7-60.3] vs. 55.9 [50.3-61.1] %; active LAEF 40.2±8.6 vs. 43.1±7.8%). LA global longitudinal strain in the active phase was increased (16.3±4.1 vs. 17.8±4.2%). The effect of spironolactone was similar in patients with high (N = 18) and normal (N = 18) aldosterone status (defined by plasma renin activity and 24-h urine aldosterone). Treatment of RHTN with spironolactone is associated with improvements in LA size and function, and atrioventricular coupling, regardless of whether aldosterone levels were normal or high at baseline. This study suggests the need for larger prospective studies examining effects of mineralocorticoid receptor antagonists on atrial function and atrioventricular coupling.

Echocardiographic parameters indicating left atrial reverse remodeling after catheter ablation for atrial fibrillation.

The echocardiographic parameters total atrial conduction time (PA-TDI duration), left atrial (LA) volume index (LAVI), and LA strain reflect adverse atrial remodeling and predict atrial fibrillation (AF). The aim of this study was to investigate echocardiographic parameters indicating reverse LA remodeling and potential associations with AF recurrence after pulmonary vein isolation (PVI). This prospective observational study consecutively enrolled patients scheduled for PVI for symptomatic AF. Electrocardiogram (ECG) test and transthoracic echocardiography were performed the day before and after PVI and again 3 months later. AF recurrence was determined by Holter ECG at 3 months, and telephone follow-up at 12 months, after PVI. The parameters of LA remodeling [PA-TDI, LAVI, and LA strain analysis: reservoir strain (LASr), conduit strain (LAScd), contraction strain (LASct)] were determined by transthoracic echocardiography. A total of 48 patients were included in the study (mean age: 61.4 ± 12.2 years). PA-TDI significantly decreased the day after PVI compared with the baseline (septal PA-TDI 103 ± 13 vs. 82 ± 14.9 ms, p ≤ 0.001; lateral PA-TDI 122.4 ± 14.8 vs. 106.9 ± 14.4 ms, p ≤ 0.001) and at the 3-month follow-up (septal PA-TDI: 77.8 ± 14.5, p ≤ 0.001; lateral PA-TDI 105.2 ± 16.1, p ≤ 0.001). LAVI showed a significant reduction at the 3-month follow-up compared with the baseline (47.7 ± 14.4 vs. 40.5 ± 9.7, p < 0.05). LASr, LAScd, and LASct did not change after PVI compared with the baseline. AF recurred in 10 patients after PVI (21%). Septal PA-TDI, septal a', and LAVI/a' determined the day after PVI were associated with AF recurrence. Changes in echocardiographic parameters of LA remodeling and function indicate that functional electromechanical recovery preceded morphological reverse remodeling of the left atrium after PVI. Furthermore, these changes in echocardiographic parameters indicating LA reverse remodeling after PVI may identify patients at high risk of AF recurrence.

Predictive value of a comprehensive atrial assessment with cardiac magnetic resonance in non-ischemic cardiomyopathy: keep it simple.

Cardiac magnetic resonance (CMR) can provide a multi-parametric evaluation of left atrial (LA) size and function. A complete CMR-based LA assessment might improve the risk stratification of patients with non-ischemic dilated cardiomyopathy (DCM). We performed a comprehensive CMR-based evaluation of LA size and function, in order to assess the prognostic impact of specific LA parameters in DCM. Secondary analysis of a prospective registry (UHSM-CMR study, NCT02326324) including 648 consecutive patients with DCM and CMR evaluation of LA area and LA length. Of these, 456 had complete LA assessment covering reservoir, conduit and booster pump function and including LA reservoir strain evaluated with feature tracking. The heart failure (HF) endpoint included HF hospitalizations, HF death and heart transplant. The arrhythmic endpoint included ventricular arrhythmias (VA) (sustained or treated by implantable defibrillator) and sudden death (SD). At median follow-up of 23 months, 34 patients reached the HF endpoint; in a multivariable model including NYHA class and LVEF, LA length had incremental predictive value. LA length ≥ 69mm was the best cut-off to predict HF events (adjusted HR 2.3, p = 0.03). Among the 456 patients with comprehensive LA assessment, only LA length was independently associated with the HF endpoint after adjusting for LVEF and NYHA class. By contrast, no LA parameter independently predicted the arrhythmic risk. In DCM patients, LA length is an independent predictor of HF events, showing stronger association than other more complex parameters of LA function. No atrial parameter predicts the risk of VA and SD.

Left atrial strain as an independent predictor of sinus rhythm maintenance after catheter ablation for paroxysmal atrial fibrillation in HFpEF patients

Abstract Background The early AF treatment by radio-frequency catheter ablation (CA) is very important for improving clinical outcome in patients with history of atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). Left atrial (LA) strain showed to be a useful index to monitor atrial function in AF and HFpEF states. However, the accuracy of LA strain to predict the long-term maintenance of sinus rhythm (SR) in HFpEF patients with paroxysmal AF undergoing CA is still under debate. Aims To define the best echocardiography derived parameters to predict the long-term maintenance of SR in paroxysmal AF patients with high probability of HFpEF undergoing CA. Methods We prospectively enrolled 200 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%). All patients had a H2FPEF score suggesting high probability of HFpEF. During sinus rhythm, all patients underwent comprehensive transthoracic echocardiography at baseline, including assessment of left ventricular (LV) global longitudinal strain (GLS), left atrial (LA) reservoir strain (LASr), LA conduit strain (LAScd) and LA contractile strain (LASct) using two-dimensional speckle tracking in apical views. Results After 42+/-8 months follow-up, a total of 34 (17%) patients had a documented recurrence of AF. Patients with AF recurrence had lower LASr (22.2% vs. 28.3%, p &amp;lt; 0.001) and LASct (10.9% vs. 13.2%, p &amp;lt; 0.01) compared to patients who keep on SR. Among speckle tracking derived LA phasic strain indices, LASr showed the largest area under the curve (AUC = 0.8, p &amp;lt; 0.001) and the strongest independent predictive value (LASr &amp;gt; 22%) of long-term maintenance of SR with sensitivity of 80% and specificity of 66% (Figure 1). Other parameters of LA function, LA diameter, maximum or minimum LA volume index, LV GLS or ejection fraction, and indices of LV diastolic function had lower area under the curve. Using multivariable logistic regression, only LASr (OR 0.89, 95% CI 0.81-0.97, p=0.013) was independently associated with long-term SR maintenance while other LA size and function indices were not. Conclusion In HFpEF patients with paroxysmal AF undergoing CA, LASr is more accurate predictor of SR maintenance than other standard echocardiographic parameters in long-term follow-up.