Left Atrial Strain Research Articles

Arterial-myocardial coupling in primary AL amyloidosis. A validation study of vascular involvement

Abstract Background Primary AL amyloidosis is a rare yet lethal systemic disorder. Previously published own and others’ work indicated that vascular involvement in AL cardiac amyloidosis defined as low blood pressure or paradoxical vasodilation may independently affect survival. Mechanistic data will pave the way to validate the clinical role of vascular involvement in these patients. Purpose We sought to explore the presence of arterial-myocardial coupling in AL amyloidosis by investigating associations between markers of vascular and cardiac involvement. Methods We consecutively recruited n=152 newly diagnosed patients with AL amyloidosis that underwent thorough vascular examination including reactive vasodilation (flow mediated vasodilation, FMD and vasodilation in response to cold-pressor test) using high resolution ultrasonography. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) and aortic pressures and markers of arterial wave reflections were estimated using radial artery tonometry. In a subgroup of patients, transthoracic echocardiography (n=152) and cardiac magnetic resonance (CMR) (n=59) were performed. Results Vascular reactivity correlated with global longitudinal strain (GLS), left ventricle ejection fraction (LVEF)/GLS ratio and worse LV volumes. Vasodilation post-cold pressure test was correlated with LV mass. cSBP exhibited a negative correlation with markers of heart involvement, wall thickness markers, GLS, and CMR tissue characterization markers. A positive correlation between cSBP and LVEF, rotation and twist strain, myocardial work and contractility markers and late gadolinium enhancement (LGE). cDBP was associated with systolic function and contractility markers, with myocardial work indices and LGE. A negative relationship with GLS, LA strain, RV GLS and LA diameter and E/e’ was noted. In addition, T2 was negatively correlated with cDBP. SBP was correlated positively with LVEF, contractility markers, and LGE myocardium and negatively correlated with biomarkers of heart involvement, GLS, CMR structure and tissue characterization. DBP was positively correlated with LGE and myocardial work. A negative relation with NTproBNP, E/e’, RVSP, LA diameter and T2 mapping was noted. Time of wave reflections (Tr) was negatively correlated with rotation strain and positively correlated with circumferential strain, LA strain and LV structure. Ai@75 was positively correlated with myocardial work and contractility markers, and LGE. Ai@75 was negatively correlated with markers of heart involvement, LV structure, E/e’, worse GLS and adverse CMR tissue characterization. Conclusion Markers of peripheral vascular dysfunction were associated with cardiac structure and function acquired both with echocardiography and CMR in AL amyloidosis. This arterial-myocardial coupling supports the clinical role of peripheral vascular involvement in this disease and warrants further investigation.

Left atrial reservoir strain and global longitudinal strain associates with re-hospitalization and mortality in patients admitted for acute heart failure

Abstract Background Left atrial reservoir strain (LAr) and global longitudinal strain (GLS) have emerged as useful parameters for the assessment of left ventricular diastolic function and the estimation of left ventricular filling pressures. Yet, there remains a gap of knowledge regarding the possible association of LAr and GLS with re-hospitalization and mortality in patients with acute heart failure (HF). Aims This study aims to investigate the association between LAr and GLS with re-hospitalization and mortality in patients admitted for acute HF. Methods Out of 526 enrolled patients admitted for acute HF, 142 (mean age 71, 25% women) were systematically evaluated for LAr and GLS using speckle tracking echocardiography. Multivariable Cox regression analyses, adjusting age, sex, current smoking prevalent atrial fibrillation, hypertension, kidney disease and plasma glucose, were used to assess the associations between continuous values of LAr and GLS with all-cause mortality and HF-related re-hospitalization. Results The median follow-up time to death of any cause and HF rehospitalization was 39 (interquartile range 14-66) and 22 (4-51) months, respectively. During follow up, 63 (44%) patients died, and 63 (44%) were re-hospitalized due to HF. Lower values of LAr were significantly associated with higher risk of mortality (HR 0.93; 95%CI 0.89-0.98, p=0.008). Similarly, lower GLS was associated with higher risk of mortality (HR 0.94; 95%CI 0.89-0.99, p=0.045). Only lower values of LAr were associated with higher risk of HF re-hospitalization in the multivariable model (HR 0.93; 95%CI 0.88-0.98, p=0.004). Conclusion In this prospective, long-term follow-up study of patients with acute heart failure, lower values of LAr and GLS showed prognostic significance, with lower values being indicative of poorer outcomes. Notably, LAr was associated with higher risk of both death and rehospitalization for heart failure, whereas GLS was solely associated with higher mortality risk. These echocardiographic parameters could be further investigated for risk assessment of patients with heart failure in order to identify those at higher risk of rehospitalization and death, thereby facilitating targeted interventions to improve their prognosis.KM-curves for or the Quartiles of LAr

Enhanced diagnostic accuracy of cardiovascular magnetic resonance in identifying heart failure with preserved ejection fraction through assessment of right ventricular systolic dysfunction

Abstract Backgrounds Right ventricular maladaptive response to increased afterload affects exercise performance in heart failure with preserved ejection fraction (HFpEF). We investigated its role in the diagnosis of early stage of HFpEF with cardiac magnetic resonance (CMR) and invasive cardiopulmonary exercise testing (iCPET). Methods One hundred forty-five patients with suspected HFpEF were prospectively recruited from two centers and 113 of them completely underwent echocardiography, iCPET, and CMR. The diagnosis of HFpEF was based on the result of iCPET (pulmonary capillary wedge pressure > 15mmHg at resting and >25mmHg at peak exercise). Area under the curve (AUC) was determined by comparing HFpEF with non-HFpEF patients. Results Seventy-two HFpEF (68±10 years) and forty-one non-HFpEF (66±11 years) were identified. The resting pulmonary artery compliance was significantly reduced in HFpEF. CMR right ventricle longitudinal strain and left atrial reservoir strain had the highest diagnostic accuracy (AUCs 0.805 and 0.776, respectively). There is a sex disparity in the diagnosis accuracy of left atrial (LA) reservoir strain, with male patients exhibiting a significantly increased AUC (0.801) compared to females (AUC 0.559). Conclusions Right ventricular systolic dysfunction is an early indicator of HFpEF, accompanied by impaired LA filling. The diminished LA filling may be more prevalent in male patients, suggesting distinct early pathophysiological progressions between genders.

Prognostic value of left atrial and ventricular strain in moderate atrial and ventricular secondary mitral regurgitation

Abstract Background Secondary mitral regurgitation (SMR) is associated with increased morbidity and mortality. In these patients, left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS) have been proposed to improve risk stratification. However their prognostic value was shown to be inconsistent when considering the SMR etiology (i.e. atrial or ventricular), possibly due to be the influence of atrial fibrillation (AF) on these measures and specifically LARS. Moreover, data focusing on moderate SMR is lacking. Aim To investigate the prognostic value of LVGLS and LARS in patients with SMR stratified according to etiology, and to identify optimal threshold for both measures. Methods Patients (n=1061; age 68±11years , 59% male) with moderate SMR were retrospectively included and classified as ASMR or VSMR, and further subdivided into "sinus rhythm (SR) subgroup" (ASMR-SR: n=68 , VSMR-SR: n=435) or as "AF subgroup" (ASMR-AF: n=284 , VSMR-AF: n=274), if patients had history of AF. The endpoint was a composite of heart failure events and all-cause mortality. Threshold values for LVGLS and LARS were defined based on spline curve analysis. Results As compared to VSMR, ASMR patients were more frequently female (61% vs. 35%, p<0.001), had less comorbidities and were less symptomatic (i.e. NYHA functional class III-IV in 11% of ASMR vs. 24% of VSMR, p<0.001). For the echocardiographic characteristics, VSMR patients showed lower LV ejection fraction and LVGLS, as compared to ASMR patients. For both ASMR and VSMR, patients in the AF subgroups had larger LA volume index, lower LARS and more severe tricuspid regurgitation (Figure 1). During a median follow-up of 78 (IQR: 44-111) months, 27% of ASMR-SR, 37% of ASMR-AF, 50% of VSMR-SR and 72% of VSMR-AF group reached the combined endpoint. Separated multivariable cox regression analyses were performed in ASMR and VSMR patients (Table 1): for both etiologies, LARS and LVGLS were independently associated with the endpoint after correcting for other significant variables at the univariate analysis, including the SR or AF group and the interventions during follow-up. In addition, a stepwise addition of LVGLS and LARS to a basic model led to a significant difference in the likelihood ratio for both groups. The thresholds of LVGLS and LARS associated with an increased risk of the combined endpoint differed per etiology. For LVGLS the threshold was <16% for ASMR, and <12% for VSMR. When considering LARS assessment, different thresholds were identified according to the SR or AF group: <18% in ASMR-SR; <15% in ASMR-AF; <17% in VFMR-SR and <12% in VFMR-AF. Conclusion In moderate SMR patients, LVGLS and LARS are independently associated with outcomes both in ASMR and VSMR and could be considered to improve risk stratification. However, lower threshold for both parameters should be considered based on etiology and on the presence of AF.

Is left atrial reservoir strain a superior modality to predict acute left ventricular failure in hypertensive patients

Abstract Background The left atrium (LA) plays an important role in the pathophysiology of heart failure. Left Atrial function has 3 components and their relative contributions, under normal circumstance, include reservoir(40%), conduit (35%), and active pump(25%) function(1). All these functions can be assessed by their respective strain, measured in trans thoracic echocardiography usually by speckle tracking, from apical 4 and 2 chamber views. Of the 3 types of LA strain, LA reservoir strain (LAS-r), is the best reflection of atrial function(2). LA strain can detect LA dysfunction even before obvious LA enlargement, aiding preclinical diagnosis of cardiac dysfunction. Purpose To assess if Left atrial reservoir strain was a superior modality to predict acute Left Ventricular Failure in hypertensive patients. Methodology Our study cohort consisted of 200 hypertensive patients, 84 females and 116 males, 40 to 71 years old with hypertension duration of 6 months to 21 years .Patients with other co morbidities were excluded. All were on treatment and had BP ranging from normal to high. Sixty two (31%) had experienced one or more episodes of acute left ventricular failure(LVF). Patients underwent in addition to routine investigations, detailed ECHO including measurement of left ventricular global longitudinal strain(LVGLS- normal > -18) and LAS-r (Normal >35). Results and Discussions All patients had normal ejection fraction. 128 (64%) had LVDD. 102(79.8%) had grade 1 LVDD, 24 (18.6%) had grade II LVDD and 2 (1.6%) had Grade III. Forty eight (37.5%) of the 128 with LVDD experienced acute LVF and 23(47.9%) of them had grade 11 LVDD or more. Forty two (21%) had reduced LVGLS, of these, 18(42.9%) experienced acute LVF and of these, 14(77.8%) had in addition reduced LAS-r. One hundred and two (51%) had reduced LAS-r (LAS-r <25), of which 61(59.8%) had experienced acute LVF. 63(31.5%) had increased LA volume of which 37( 58.7%) had experienced acute LVF. 5.7% of patients with BP <150/90 had reduced LAS-r, 69.5% with BP between 150/90- 169/100 had reduced LAS-r and 85.4% with BP > 170 had reduced LAS-r. Of the 62 patients with acute LVF, 18(29%) showed reduced LVGLS, 48(77.4%) had LVDD, 37(59.7%) had increased LA volume and 61(98.4%) had reduced LAS-r indicating that the latter was an earlier, better predictor of acute LVF than the former three. Although there were no age or gender differences in the findings, the prevalence of reduced LAS-r was higher with less well controlled BP. Conclusions In our study, LAS-r, irrespective of the age or sex, was an earlier better predictor of acute LVF than reduction of LVGLS, LVDD or increased LA volumes, in hypertensive patients. The prevalence of reduced LAS-r was higher in patients with poorly controlled BP. Prognostic significance of LAS-r can help influence early clinical decision making and for defining early management.TABLE 1TABLE 2

Left atrial reservoir strain as a prognostic indicator for cardiovascular events after mitral valvuloplasty

Abstract Background In patients after mitral valvuloplasty (MVP), assessing valve function and heart failure (HF) is crucial for prognostic predictions. Left ventricular diastolic function assessed by transthoracic echocardiography (TTE) plays an important role in the evaluation of HF in general practice. However, post-mitral valve surgery patients are excluded from the left ventricular diastolic function assessment guidelines proposed by the American Society of Echocardiography in 2016 due to their low correlation with left ventricular diastolic function indices. On the contrary, the left atrial reservoir strain (LARS) before MVP is considered as a prognostic factor, reflecting left atrial dysfunction caused by mitral regurgitation. Nevertheless, there are limited reports on the relationship between LARS and cardiovascular (CV) events after MVP. Purpose The study aims to investigate the utility of LARS in predicting CV events after MVP. Methods The study included 249 patients who underwent TTE between January 2011 and January 2023 after MVP at our hospital. Patient background data, including NYHA classification, medical history, medications, blood tests, and TTE data, were collected at the time of follow-up TTE. LARS, left ventricular global longitudinal strain (LV-GLS), and right ventricular free wall strain (RV-FWSL) analysis were performed using a vender-independent external strain analysis software for all patients in the cohort. The primary endpoints were cardiovascular death and HF rehospitalization. The predictor of cardiovascular events was assessed using the Cox proportional hazards model and Kaplan-Meier curve (KMC). Results The mean age was 61±14 years, and 159 patients (64%) were male. The median time from surgery to TTE was 4.8 (1.0-6.8) years, 32 patients (13%) had events within 8.5 (3.7-10.8) years after TTE. The event groups had higher age, NYHA classification, and NT-pro BNP compared to the non-event group. TTE parameters such as left ventricular mass index, left ventricular end-diastolic volume and end-systolic volume were larger, and LV-GLS and LARS were significantly lower in the event group. In multivariate Cox proportional hazards models showed that LARS was also a prognostic indicator even after adjustment for several variables (Table 1). The KMC showed that LARS was associated with events regardless of left atrial volume index (Log-rank p <0.001, chi-square:31.03) (Figure 1). Conclusion LARS was strongly associated with CV events after MVP. We consider LARS to be a useful prognostic indicator after MVP.

Performance of an automated echocardiographic artificial intelligence model. to detect subclinical heart failure with preserved ejection fraction (HFpEF) in community-dwelling older adults

Abstract Background Heart failure (HF) with preserved Ejection Fraction (HFpEF) is common among older adults and associated with a high burden of morbidity and mortality. Early identification of subclinical HFpEF, defined by abnormalities in cardiac structure and function without symptoms of HF, can prompt early initiation of evidence-based therapies to prevent HFpEF. However, scalable strategies for the identification of subclinical HFpEF are lacking. Purpose To evaluate the performance of a validated, automated echocardiographic artificial Intelligence algorithm (Ultromics, UK) to identify subclinical HFpEF among community-dwelling individuals without HF. Methods The study included participants of the Dallas Hearts and Minds Study without HF who underwent cardiovascular phenotyping with resting and exercise echocardiography and maximal cardiopulmonary exercise testing. The resting apical 4C echocardiographic images were analyzed by the AI echo algorithm to identify the HFpEF phenotype (AI-HFpEF). Subclinical HFpEF was defined by E/e’ >14 and Peak exercise oxygen uptake (VO2peak) <25th percentile for the cohort. The performance of the AI algorithm to detect subclinical HFpEF was determined using the area under the receiver operating curve and decision curve analysis and was compared with the previously validated H2FpEF score. The association between the AI-HFpEF phenotype and the presence of subclinical HFpEF, VO2peak, exercise E/e’, left ventricular strain, and left atrial strain was assessed using multivariable-adjusted logistic and linear regression models. Results The study included 511 participants (mean age: 61 y, 57% women, mean VO2peak = 16.9 ml/kg/min). Using the AI echo algorithm, subclinical HFpEF was detected in 10% of participants (n=76), and 10% were non-diagnostic. The participants with (vs. without) AI-HFpEF phenotype were older and had a higher burden of CVD risk factors, left ventricular hypertrophy, and left atrial dilation. Subclinical HFpEF, as defined by the gold standard criteria, was present in 5.3% of participants. The AUROC for diagnosis of subclinical HFpEF using the AI-HFpEF algorithm was 0.85 vs. 0.78 by the H2FpEF score (see Figure). In the adjusted analysis, the AI-HFpEF phenotype was significantly associated with greater odds of subclinical HFpEF by exercise and echocardiographic phenotyping criteria, higher E/e’ with exercise, lower VO2 peak, and worse LV and LA strain (see Table). In decision curve analysis, the AI-HFpEF algorithm identified 23 additional cases of subclinical HFpEF per 1000 screened participants compared with the H2FpEF score. Conclusion The AI-HFpEF algorithm can reliably identify community-dwelling individuals with subclinical HFpEF characterized by diastolic dysfunction at rest or exercise and impaired exercise capacity. Future studies are needed to assess the utility of the AI-HFpEF algorithm in screening for subclinical HFpEF in health systems.

Decreased left atrial volume and preserved left atrial function in children with congenital Zika syndrome

Abstract Introduction The infection caused by Zika virus during pregnancy leads to congenital Zika syndrome (CZS). In a previous study of our group, we found that the heart is smaller in children with CZS, with few functional alterations. Left atrial strain imaging enables quantitative assessment of left atrial function, and recently its application has also shown promise in the pediatric population. Purpose To evaluate left atrial function in children affected by CZS, using echocardiogram and speckle tracking imaging technique. Methods This observational study was conducted with children with CZS using a two-dimensional speckle tracking technique to measure left atrial reservoir strain (LAS-r), conduit strain (LAS-cd), and contraction strain (LAS-ct). Also, to investigate the relationship between LAS-r and systolic excursion of the septum and lateral mitral annular plane (MAPSE), left atrial volume index and E/e’ ratio. Results A total of 52 patients were included, the median age of the studied population was 5 years (3 to 6), 59.6% male, and the body surface area was 0.66 [0.51, 0.90]. In the echocardiographic evaluation the left atrium volume index (ml/m²) was 13.15 [6.80, 18.00], considered smaller by the reference value. Also, the LAS-r (%) was 40.99 [24-70.5], LAS-cd (%) was 30,94 [32.5-52.5], LAS-cd (%) was 10,91 [5.2-24], values considered normal by the literature. Lateral MAPSE (cm) was 1.25 [0.81, 1.86] and septal MAPSE (cm) was 0.98 [0.78, 1.66] and E/e' ratio was 7.52 [4.57, 10.78]. A positive linear correlation was found between LAS-r and lateral MAPSE (r = 0.51, P = 0.019). Conclusion This original study with children with CZS shows that despite reduced atrial volume, the left atrial function remains normal, and correlates with left ventricular function evaluated by MAPSE. Further studies are needed to prospectively analyze the follow-up of left atrial morphology and function in this population.

Left atrial strain predicts adverse events in hypertrophic cardiomyopathy: preliminary results from a CMR study

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of major adverse cardiovascular events (MACE), however, current risk stratification methods are imperfect. Left atrial global longitudinal strain (LA GLS) is an increasingly acknowledged predictive parameter, yet its potential role in HCM is not well defined. Purpose This study aims to investigate the prognostic role of cardiac magnetic resonance (CMR)-derived LA GLS for the occurrence of MACE in patients with HCM. Methods A retrospective, single-centre, CMR study of HCM patients was conducted. Clinical data was collected from electronic medical record and CMR images were analysed by two blinded investigators. LA GLS was derived from CMR two-chamber cine images by a semiautomatic method, and was categorized according to its median value. The endpoint was a composite of MACE, including all-cause death, sudden cardiac death (SCD), sustained and non-sustained ventricular tachycardias (VT), appropriate implantable cardiac defibrillator (ICD) shocks, heart failure (HF) hospitalization, and new-onset atrial fibrillation (AF). Cox regression analysis was performed. The preliminary results of the study are now reported. Results A total of 54 HCM patients were included, mean age was 58.5 years ± 15.9 and 38.9% were female. Average maximal wall thickness (MWT) was 18.0 mm ± 3.9, 37% had left ventricular outflow obstruction (LVOTO) and 45.1% had positive late gadolinium enhancement (LGE). After a mean follow-up of 6.9 ± 3.0 years, 26 patients (48.1%) experienced the composite endpoint. Figure 1 shows the clinical and CMR differences according to the occurrence of MACE. LA GLS was significantly lower in patients with MACE compared to those without (26.5 ± 19% vs 36.7 ± 13%, p=0.026), with a moderate predictive value (AUC = 0.68, Figure 2A). Multivariate Cox regression analysis revealed that a decrease in LA GLS (HR 1.09 per each 1% decrease, 95% CI 1.03-1.15, p=0.002), the presence of LGE (HR 6.9, 95% CI 1.7-28, p=0.007), the presence of LVOTO (HR 3.4, 95% CI 1.12-10.2, p=0.031) and an increase in MWT (HR 1.23 per each 1mm increase, 95% CI 1.05-1.45, p=0.011) were independently associated with MACE. Among low-risk HCM patients (absence of LGE or LVOTO, or MWT below our median value), LA GLS had an additional prognostic role, and those with an LA GLS above the median value (LA GLS>29.7%) presented a remarkably favourable prognosis (Figure 2B-D). Conclusions CMR-derived LA GLS is a predictor of outcomes in HCM beyond established imaging prognostic factors. Particularly, LA GLS appears to be useful in risk-stratifying low-risk HCM patients: those with normal LA GLS show an excellent prognosis. If confirmed in larger studies, LA GLS could be used to individualise HCM management.Figure 2

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.

Right atrial strain: the hidden proof of bi-atrial cardiomyopathy in AF patients?

Abstract Background Although assessment of left atrium (LA) abnormalities has been extensively studied in atrial fibrillation (AF), structural and functional changes in the right atrium (RA) have remained almost unexplored in this context. Purpose We investigated the role of bi-atrial strain in patients with AF undergoing catheter ablation (CA). Methods Fifty-six consecutive patients undergoing catheter ablation of AF were prospectively studied with speckle-tracking echocardiography and electrophysiological study, before and after CA (median follow-up: 7±3 months). A group of 32 subjects undergoing CA of paroxysmal atrioventricular node-reentrant tachycardia, without structural heart disease, served as control group. Results Patients with AF had worse LA, but also RA strain indexes compared to controls [RA strain parameters: peak RAS reservoir (pRASr): 22.1±12.6 vs 29.8±12.7%, p=0.009; RA dispersion: SD-regional-RA-time-to-peak (SD-regional-RA-TTP): 0.048±0.015 vs 0.038±0.009, p=0.020)]. Patients with persistent AF showed similar LA strain values, but worse RA strain indexes, compared to patients with paroxysmal AF (pRASr: 24.8±12.1 vs 15.9±11.7%,p=0.017; SD-regional-RA-TTP:0.043±0.023 vs 0.062±0.030, p=0.016). RA function showed a significant relation with both LA strain and volume indexes and with abnormal LA electroanatomical substrate (pRASr and pLASr, Pearson correlation: r 0.594, p< 0.001; pRASr and low-voltage LA area: -0.316, p=0.018). RA, but not LA, parameters were found significantly reduced in patients with AF recurrence post-CA compared to those who maintain sinus rhythm (pRASr: 14.1±11.7 vs 24.6±13.5, p=0.039; SD-regional-RA-TTP: 0.054±0.031 vs 0.032±0.010, p=0.002), while the only independent clinical predictor of AF recurrence remained cardiovascular risk profile (CHA2DS2 VASc Score: HR 1.47,CI 1.003-2.158, p= 0.048). Conclusion RA function, as assessed by strain imaging, resulted progressively impaired in worse subtypes of AF, showing a strong correlation with bi-atrial mechanical and electroanatomical parameters, and associated with AF recurrences post-ablation.Graphical Abstract

Comparative analysis of the 2016 diastolic guidelines and left atrial stiffness in predicting exercise tolerance and cardiac events

Abstract Background While the 2016 ASE/EACVI guideline for diastolic dysfunction is a robust tool for prognostication, their complexity and 20% rate of indeterminate limit their routine clinical practice. Purpose Left atrial (LA) stiffness, calculated as the E/e' ratio divided by LA strain, provides a simpler measure that indirectly reflects LA pressure. This study aims to evaluate whether LA stiffness can be better than the 2016 guidelines in predicting poor exercise tolerance and cardiac events (cardiac death or heart failure hospitalization) in patients with dyspnea. Methods In this retrospective single-center cohort study, 404 patients who underwent echocardiography and cardiopulmonary exercise test simultaneously were reviewed. Poor exercise tolerance was defined by a peak oxygen uptake (VO2) of <14 ml/kg/min or a minute ventilation-carbon dioxide production (VE/VCO2) slope of ≥ 40. The predictive abilities of LA stiffness for peak VO2, VE/VCO2 slope, and cardiac outcomes (cardiac death or heart failure hospitalization) were compared to those of the 2016 guidelines using ROC curve analysis. Results The mean left ventricular ejection fraction was 50% (IQR 58.58-66.70). Of the 404 patients (mean age 58.51, male 50.74%), peak VO2 < 14 and VE/VCO2 ≥ 40 were observed in 38 and 24 patients, and cardiac events occurred in 37 patients during median follow up of 85.45 months. ROC analysis showed that LA stiffness had AUC values of 0.697 (95% CI: 0.604-0.789) for peak VO2 < 14, 0.645 (95% CI: 0.529-0.760) for VE/VCO2 slope ≥ 40, and 0.628 (95% CI: 0.541-0.715) for cardiac events. The 2016 guidelines achieved AUCs of 0.685 (95% CI: 0.604-0.766), 0.586 (95% CI: 0.481-0.690), and 0.589 (95% CI: 0.505-0.674). Statistical comparison revealed no significant difference between the predictive capabilities of LA stiffness and the 2016 guidelines (p-values: 0.735, 0.165, and 0.439, respectively). (Figure) Conclusion LA stiffness offers comparable diagnostic accuracy to the 2016 ASE/EACVI guidelines in assessing poor exercise tolerance and cardiac events in patients with dyspnea. Given its simplicity and ease of measurement, LA stiffness represents a viable alternative for evaluating diastolic dysfunction.ROC curve

Prognostic value of left atrial strain in patients with moderate to severe mitral stenosis

Abstract Background Mitral stenosis causes an inflow restriction during diastole and is characterized by an increase in left atrial (LA) pressure with reduced cardiac output. Pressure overload of the LA can lead to atrial fibrosis and remodeling, resulting in a loss of LA reservoir and compliance capacity that can lead to backward load on the pulmonary circulation. To date, there are limited studies evaluating the impact of LA strain on prognosis of mitral stenosis patients. Purpose The aim of this study was to assess the prognostic value of LA strain in patients with moderate to severe mitral stenosis using two-dimensional (2D) strain imaging. Methods This was a single-center retrospective study, 237 patients with moderate or severe mitral stenosis were enrolled from January 2010 to December 2022. Baseline clinical and echocardiographic parameters were collected, LA strain measurements with reference time point at end diastole for reservoir strain (LASr), conduit strain (LAScd) and contraction strain (LASct) were analyzed using TOMTEC software. The endpoint was a composite outcome of all-cause mortality, heart failure hospitalization and valve intervention (percutaneous transvenous mitral commissurotomy and surgical intervention). All the LA parameters were analyzed separately to avoid collinearity. Results A total of 237 patients were included in the study. The patients had a mean age was 66.56 ± 13.61 years-old and were predominantly female (67.9%) with median follow up duration is 4.54 years (IQR 1.44 – 6.44). Mean left ventricular ejection fraction (LVEF) was 56.86 ± 10.51%, mean left atrium volume index (LAVI) was 73.94 ± 55.46 ml/m2, mean for LASr, LAScd and LASct were 11.81 ± 8.89%, -6.19 ± 4.50%, and -5.58 ± 6.05% respectively. LASr with a cut-off < 15.8% was independently associated with the composite outcome of all-cause mortality, heart failure hospitalization and valve intervention on multivariable Cox regression analysis (HR 2.51, 95% CI 1.54 - 4.10, p < 0.001). LAScd, LASct and LA volume index did not demonstrate any significant association with the endpoint. Conclusion LASr was independently associated with all-cause mortality, heart failure hospitalization and valve intervention in patients with moderate to severe mitral stenosis.

LA reservoir strain predicts elevated left atrial pressure in patients with Veno-Arterial (VA) extracorporeal membrane oxygenator (ECMO) support for cardiogenic shock

Abstract Background Veno-arterial (VA) extracorporeal membrane oxygenator (ECMO) is not a left ventricular (LV) support system as it increases aortic pressure and LV afterload due to retrograde blood flow in the aorta. This can lead to complications such as increased LV volume (LV distention), increased LV and left atrial (LA) pressures, and pulmonary edema. We sought to investigate the correlation between LA strain and invasive LA pressure (LAP) in patients with ECMO support for cardiogenic shock undergoing atrial septostomy with stenting. Methods and Results A total of 24 consecutive patients (52±20 years; 83% were male) undergoing atrial septostomy with stenting while being on ECMO support for cardiogenic shock for left heart decompression were analyzed. LAP was measured immediately after transeptal puncture and before deployment of interatrial septal stent. A comprehensive echocardiogram was performed in all patients prior to atrial septostomy. Median time difference between echocardiogram and LAP measurement was 3.5 (0.5-20) hours. LA strain analysis was performed using the TomTec Arena 2D-cardiac performance analysis (CPA) software. LA reservoir strain was measured at peak systole during the reservoir phase in a single apical 4-chamber view. Intraclass correlation coefficients between 2 different investigators were excellent (All> 0.95). Median LA reservoir strain and LAP were 3.2 (0.5-1) % and 23 (8-53) mmHg, respectively. LA reservoir strain significantly correlated with LAP (r=0.53, p=0.034). LA reservoir strain of < 1.5% can effectively predict markedly elevated LAP (LA> 30 mmHg) (OR =9.9, p =0.0016). Conclusions LA reservoir strain significantly correlated with invasive LAP. With the advent of strain imaging software, LA reservoir strain is a feasible, reproducible, noninvasive, and straightforward method to predict the need for left heart decompression and/or to guide optimal afterload management in patients with VA-ECMO for cardiogenic shock. Further a prospective simultaneous echocardiographic and invasive LAP study is needed.

Blood pressure in the early 40s impacts left atrial function by speckle-tracking strain two decades later: data from the ACE 1950 Study

Abstract Background With higher age, the left atrial (LA) wall stiffens, giving rise to impaired reservoir function and a compensatory increase in contractile function. The exposure of systemic blood pressures (BP) through life on the left heart chambers may be an explanation, but long-term follow-up studies are lacking. LA phasic function can be quantified by echocardiographic speckle-tracking strain analysis and provide prognostic information in cardiovascular disease. Purpose To explore the impact of BP in the early 40s on LA function assessed by strain two decades later. Methods A total of 3,706 individuals born in 1950 and residing in Akershus County, Norway, were included in the Akershus Cardiac Examination (ACE) 1950 Study. Baseline examinations were conducted between 2012-2015 and included echocardiography. Of those with available echocardiographic LA strain analyses, 2,399 participants had demographic and clinical data available from the Age 40 Program, a cardiovascular health survey performed when the participants were 40 years old. We assessed the impact of BP at age 40 on LA strain two decades later. Differences in LA reservoir (LASr) and contractile strain (LASct) between systolic (<120, 120-140 and >140mmHg) and diastolic (<70, 70-90, and >90mmHg) BP groups were assessed by ANOVA. Linear regression analyses were performed using BPs as continuous variables. Results Mean age of the 2,399 participants was 40.1±0.3 years at the time of the Age 40 program, and 63.9±0.6 years at the time of the ACE 1950 baseline examination. At age 40, 20.8% of participants had BP ≥140/ ≥90mmHg or used antihypertensive medication. Mean LASr was 35.1±9.2%, while mean LASct was 17.7±5.6%. LASr did not differ significantly between groups of systolic or diastolic BP. LASct, however, showed a statistically significant increase from lower to higher groups of both systolic and diastolic BP (Figure). In linear regression analyses, no associations were found between BPs and LASr, but systolic and diastolic BPs were both significantly associated with LASct (Table). The associations between BPs and LASct remained significant after adjustment for sex, BMI, daily smoking, resting heart rate and hypertension at age 40 (Table). Conclusions Higher systolic and diastolic BP in the early forties were associated with increased LA contractile function two decades later, but no significant changes in LA reservoir function were detected. This indicates contractile function as an early marker of subtle LA dysfunction.Figure.Table.

How different types of cardiomyopathy with hypertrophic phenotype affect left atrial remodeling and function

Abstract Background Left atrial (LA) dysfunction is a common feature in hypertrophic cardiomyopathies. How the underlying etiology and pathophysiology of different cardiomyopathies affects LA remodeling and function remains unexplored. Purpose The aim of our study is to investigate the influence of various cardiomyopathies with hypertrophic phenotype on LA remodeling and function. Methods Patients with left ventricular (LV) hypertrophic phenotype who underwent cardiac magnetic resonance (CMR) were included. A group of patients with a normal CMR was included as a control group. CMR acquisitions used for clinical indication of heart failure diagnosis and etiology were retrospectively analyzed to obtain LA reservoir, conduit, and booster strain, left atrioventricular coupling index (LACI) and LA sphericity. Differences between groups were assessed. To investigate the independent clinical associates of LA reservoir, conduit and booster strain, multivariable linear regression analyses were performed. Results A total of 375 individuals were analyzed including 321 patients diagnosed with LV hypertrophy and 54 patients with a normal CMR. Of the 321 patients with LV hypertrophy, 148 were diagnosed with hypertrophic cardiomyopathy (HCM), 35 with cardiac amyloidosis (CA), 41 with hypertensive cardiomyopathy (HTN) and 97 with severe asymptomatic aortic stenosis (AS). CMR LA characteristic and strain analysis results are summarized in Figure 1. The indexed LA end-systolic volume (iLAVmax), indexed LA end-diastolic volume (iLAVmin) and LA sphericity were larger in patients with CA when compared to other groups (all p<0.05). CA patients displayed more left atrioventricular uncoupling (lower LACI) when compared to individuals with HCM, HTN, AS, and controls (all p<0.001), while no significant differences were observed across other groups. CA patients exhibited lower LA reservoir and booster strains compared to the other groups (all p<0.05), whereas no significant differences were observed across other hypertrophic phenotype diseases. Age, iLAVMax and LACI were independently associated with all the three LA strain components (Figure 2, all p<0.05). Conclusions LA remodeling and function are affected differently across the various etiologies of LV hypertrophy. CA patients exhibit more pronounced atrial involvement, whereas those with HCM, asymptomatic AS, and HTN display similar patterns of atrial dysfunction and remodeling. Additionally, CMR-derived iLAVmax and LACI are independently correlated with LA function.

Association between CHA2DS2-VASc score and left atrial function by speckle tracking echocardiography in patients with sinus rhythm

Abstract Background The CHA2DS2-VASc score is a scoring system that was first used for the risk assessment of cerebrovascular or thromboembolic events in patients with atrial fibrillation (AF). The factors that constitute the CHA2DS2-VASc scoring system can all individually have an impact on LA function. The application of this scoring system can also be applied to patients without AF. The LA structural remodeling and/or functional impairment play a part in the pathogenesis and development of AF and independent of rhythm, may result in atrial hemostasis and confer a prothrombotic diathesis, resulting in thromboembolic stroke. Speckle- tracking echocardiography (STE) makes it possible to measure LA function with relatively high accuracy and at the very early stage even in the absence of LA enlargement. Purpose The aim of our study was to assess the left atrial function in patients with sinus rhythm with different CHA2DS2-VASc scores (low, moderate and high) by speckle tracking echocardiography and to identify the association between them. Methods This study was conducted using prospectively collected data (1st May, 2022 to 30th October 2022) from patients with sinus rhythm and different CHA2DS2-VASc scores (50 Low risk score patients (1 for females and 0 for males), 50 moderate risk score patients (2 for females and 1 for males) and 50 high risk score patients (≥3 for females and ≥2 for males) After obtaining an informed consent, all volunteers underwent thorough history taking, 12 lead ECG and conventional transthoracic echocardiography and speckle-tracking echocardiography. Results LA strain during the reservoir (LASr) and conduit phases (LAScd) were statistically significantly lower in the high-risk score group (33.2 ± 7.1 and 20.3 ± 5.7) than the moderate-risk score group (36.9 ± 6.1 and 23.5 ± 4.8, p = 0.005 and 0.003 respectively) and low -risk score group (40.6 ± 5.6 and 26.9 ± 3.9, p < 0.001). In addition, LASr and LAScd were statistically significantly lower in moderate- risk score group (36.9 ± 6.1 and 23.5 ± 4.8) than the low -risk score group (40.6 ± 5.6 and 26.9 ± 3.9 ,p=0.007 and 0.001 respectively). Conclusion Higher CHA2DS2-VASc scores were associated with decreased LA strain during the reservoir and conduit phases as markers of LA function with relatively high accuracy and at the very early stage even in the absence of LA enlargement.

LA strain analysis in patients undergoing atrial fibrillation ablation using cryoballoon or pulsed-field-ablation

Abstract Background Catheter ablation for atrial fibrillation (AF) is increasing as rhythm control therapy. Besides thermal ablation approaches, such as cryoballoon ablation (CBA), a novel non-thermal and tissue-specific ablation modality – pulsed field ablation (PFA) – has been introduced. Left atrial reservoir strain (LArS) has been suggested to predict arrhythmia recurrences after AF ablation. Up to now, data describing LArS in patients undergoing their first AF ablation using PFA or CBA are sparse. Purpose To compare LArS in patients undergoing first catheter ablation for AF using either PFA or CBA. Methods Patients with transthoracic echocardiography prior to their first catheter ablation for AF were included. Patients in AF during transthoracic echocardiography, with poor 2D image quality and those that did not have a transthoracic echocardiography after AF ablation were excluded. Clinical characteristics and echocardiography parameters were analyzed. LArS was measured before and after AF ablation and was correlated with the recurrence of atrial arrhythmias in the follow-up period. Results Of 267 patients undergoing their first AF ablation, 67 patients (69% male, 65 ± 11 years) fulfilled the inclusion criteria and were further analyzed. AF ablation was performed using PFA in 55% and CBA in 45% of patients. Baseline characteristics were similar in both groups. Before ablation LArS was similar for PFA (17.69 ± 6.92%) and CBA patients (19.38 ± 9.42%, P=0.45). After AF ablation, LArS did not change significantly compared to the values before (before ablation: 20.96 ± 15.9 vs. after ablation: 19.87 ± 9.38, P=0.18), irrespective of the ablation mode (PFA before: 17.69 ± 6.92%vs. PFA after: 18.06 ± 8.9%, P=0.53; CBA before: 19.38 ± 9.42% vs. CBA after: 21.08 ± 9.48%, P=0.36). After a median of 190 days [95% confidence interval: 89 - 454 days], 25 patients (37%) experienced an arrhythmia recurrence (PFA: 38%, CBA: 37%). Comparing patients with and without arrhythmia recurrences, LArS before catheter ablation was lower in those experiencing an arrhythmia recurrence (16.02 ± 6.8%) compared to those without arrhythmia recurrence (25.58 ± 20.32%, P=0.02). However, this was independent from the ablation mode (PFA: AF-recurrence: 16.51 ± 4.27 vs. no recurrence: 21.31 ± 15.9, P=0.19; CBA: AF-recurrence: 15.48 ± 9.03 vs. no recurrence: 27.34 ± 22.14, P=0.07). Univariable regression analysis - including sex, age and comorbidities - revealed a trend for baseline LArS being associated with arrhythmia recurrence (HR 0.92, 95% CI: 0.86 – 1.01; P=0.065). Conclusions This hypothesis generating study indicates that LArS is not affected by AF ablation irrespective of the ablation mode. Patients with lower LArS before ablation had more arrhythmia recurrences independent of the ablation mode. A larger patient population is needed to assess the association of LArS and arrhythmia recurrences after AF ablation using different ablation modalities.

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

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

Echocardiographic predictors of cardiovascular outcome in heart failure with preserved ejection fraction

Abstract Background The optimal echocardiographic predictors of cardiovascular outcome in heart failure with presereved ejection fraction (HFpEF) are unknown. Purpose We aimed to identify independent echocardiographic predictors of cardiovascular outcome in patients with HFpEF. Methods Systematic literature search of three electronic databases was conducted from date of inception until November 2022. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for echocardiographic variables from multivariate prediction models for the composite primary endpoint of cardiovascular death and heart failure (HF) hospitalization were pooled using a random effects meta-analysis. Specific subgroup analyses were conducted for studies that enrolled patients with acute versus chronic HF, and for those studies that included E/e’, pulmonary artery systolic pressure (PASP), renal function, natriuretic peptides and diuretic use in multivariate models. Results Forty-six studies totalling 20,056 patients with HFpEF were included. Three echocardiographic parameters emerged as independent predictors in all subgroup analyses: Decreased left ventricular (LV) global longitudinal strain (HR 1.24, 95% CI 1.10-1.39 per 5% decrease), decreased left atrial (LA) reservoir strain (HR 1.30, 95% CI 1.13-1.1.50 per 5% decrease) and lower tricuspid annular plane systolic excursion (TAPSE) to PASP ratio (HR 1.17, 95% CI 1.07-1.25) per 0.1 unit decrease). Other independent echocardiographic predictors of the primary endpoint were a higher E/e’, moderate to severe tricuspid regurgitation, LV mass index and LA ejection fraction, although these variables were less robust. Conclusion Impaired LV global longitudinal strain, lower LA reservoir strain and lower TAPSE/PASP ratio predict cardiovascular death and HF hospitalization in HFpEF and are independent of filling pressures, clinical characteristics and natriuretic peptides. These echocardiographic parameters reflect key functional changes in HFpEF, and should be incorporated in future prospective risk prediction models.