Left Atrial Strain Research Articles

Normal ranges of left atrial phasic strains and strain rates by 2D speckle-tracking echocardiography in pediatrics: a systematic review and meta-analysis

Establishing normal values of left atrial (LA) phasic strains and strain rates is essential for distinguishing between normal and abnormal functions, determining the degree of abnormality, and understanding the clinical significance of reported values in pediatrics. This meta-analysis aimed to establish normal values of two-dimensional speckle-tracking echocardiography (2DSTE)-derived LA phasic strains and strain rates in the pediatric population and identify the sources of inter-study heterogeneity for these values. A comprehensive search of PubMed, Scopus, and Embase databases was conducted using keywords such as “left atrial/left atrium,” “strain/speckle/deformation,” and “echocardiography” combined with pediatric age categories. Inclusion criteria comprised English-language human studies involving healthy subjects under 18 years of age. Subjects were categorized as neonates (up to 1 month), infants (1–12 months), and children (1–18 years). A random-effects model was applied to determine 2DSTE-derived LA strains and strain rates, and a meta-regression analysis was performed to investigate inter-study heterogeneity. Our analysis included 17 studies involving 1448 healthy subjects. For children, the mean values of LA strains during the reservoir, conduit, and contraction phases were 47.3% (95% CI 42.5–52.1%), 32.8% (95% CI 27.8–37.8%), and 12% (95% CI 10.0–14.1%), respectively. The mean values for LA strain rates were 2.4 s−1 (95% CI 1.1–3.8 s−1), 4.3 s−1 (95% CI 0.6–8.0 s−1), and 2.4 s−1 (95% CI 0.4–4.5 s−1), respectively. Inter-study heterogeneity for 2DSTE-derived LA phasic strains and strain rates was attributed to factors such as the number of study participants, publication year, software utilized, gating methods, the number of analyzed segments, the geographical region of the study, and heart rate. This study established the normal range of 2DSTE-derived LA phasic strains and strain rates. Additionally, inter-study heterogeneity was found to be influenced by various demographic, physiologic, and methodological factors.

Left atrial strain demonstrates the ability to distinguish patients with pre and post-capillary pulmonary hypertension

Abstract Background The characterization of pulmonary hypertension (PH) patients into pre or postcapillary (pcPH)phenotypes poses a challenge during screening due to the ambiguity surrounding their comorbidities. This distinction is crucial as it influences treatment decisions and prognostication. Purpose Investigating Left Atrial Strain as a Discriminant Marker for Distinguishing Pre and Post-Capillary PH. Methods Out of 164 patients exhibiting both pre- and post-capillary phenotypes, 97 had optimal left atrial 2D strain. Left atrial 2D strain was performed with a GE Vivid9 ultrasound machine equipped with dedicated software, ensuring meticulous attention to image quality and region of interest thickness restricted to a maximum of 6 mm. Subsequently, the peak left atrial strain during reservoir function was quantified as part of the investigation. To determine the optimal cut-off value, ROC curve analysis was employed. Results 60 patients had pcPH while 37 had pre-capillary PH. Mean age was 65±12y. Mean pulmonary artery pressure, wedge pressure, cardiac output and pulmonary vascular resistance averaged 40,9±10,7 mm Hg, 15,7±8,7 mm Hg, 5,9±2,0 l/min and 4,7±3,1 WU, respectively. Left atrial 2D strain ranged from +2,5% to 60%, with a mean of +18,2±11,2%. From ROC cure analysis, patients with LA 2D strain > +19,1% had a precapillary phenotype with a sensitivity and a specifity of 93% and 88% respectively (Fig 1). Left atrial 2D strain demonstrates higher sensitivity compared to various parameters, such as scores from the European Society of Respiratory Disease, left ventricular end-diastolic pressure estimation from the American Society of Echocardiography, HFA-PEFF score, and H2FPEF from the AHA. Conclusion Left atrial 2D strain demonstrates superior sensitivity in distinguishing between patients with pre and post-capillary pulmonary hypertension compared to other assessment methods.FIG 1:Left atrial 2D strainFig 2:SENS of parameters and scores

Effect of tafamidis on left atrial function in patients with transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by the functional and structural consequences of amyloid infiltration predominantly within the ventricles, causing biventricular wall thickening. Amyloid infiltration can be observed in left atrium in ATTR-CM, however, the association of left atrial (LA) myocardial function with cardiovascular events and changes in LA myocardial function with tafamidis administration have not been elucidated. Purpose The aim of this study was to identify the association between baseline LA reservoir function evaluated by left atrial reservoir strain and cardiovascular events. Furthermore, monitoring the LA reservoir function before and after tafamidis administration, we also investigated the baseline factors associated with changes in LA reservoir function in patients with ATTR-CM. Methods We studied 55 patients with biopsy-proven ATTR-CM who were started on tafamidis in our institution between July 2019 and December 2022 (age: 76 ± 2 years, male: 93%). The primary endpoint was defined as hospitalization for heart failure or cardiovascular death during a median follow-up period of 28 ± 4 months after tafamidis administration. Furthermore, we assessed the factors associated with changes in LA function before and 25 ± 3 months after tafamidis administration for 49 patients who underwent sufficient follow-up echocardiography. Results During the follow-up period, 8 patients had cardiovascular death or cardiovascular hospitalization. The Kaplan-Meier curve indicated that the occurrence of cardiovascular events for patients with LA strain ≥ the median 8.6% was significantly lower than for those with LA strain < 8.6% (log-rank P =0.002; Figure A). Furthermore, comparing LA strain before and after tafamidis administration, the group with worsening LA strain tended to be older (79.0 ± 2.0 years vs. 73.6 ± 3.3 years, P=0.004), have higher brain natriuretic peptide (350 ± 83 pg/mL vs. 199 ± 47 pg/mL, P=0.003), have lower global longitudinal strain (GLS) (9.8 ± 1.4 % vs. 12.6 ± 1.6 pg/mL, P=0.008), and higher relative apical longitudinal strain index (1.63 ± 0.4 % vs. 1.14 ± 0.2 %, P=0.021). The multivariate logistic regression analysis was that age, GLS and relative apical longitudinal strain index were the independent determinants for deterioration of LA strain after tafamidis administration (Figure B). Conclusion In our study, baseline LA reservoir function was found to be closely associated with cardiovascular events after tafamidis administration, while age, GLS and relative apical longitudinal strain index were associated with worsening LA strain after tafamidis administration. Our findings could represent an additional parameter for the effective management of patients with ATTR-CM.Figure AFigure B

Association of left atrial strain and exercise capacity among patients with hypertension: a single center study

Abstract Introduction Hypertension has been identified as one of the leading risk factors for developing cardiovascular disease in the Philippines. 1 The long term increase in afterload causes the progressive decline in both the systolic and diastolic function of hypertensive patients. There has been an increasing recognition in the role of left atrial function in the pathophysiology of several cardiac diseases, including hypertension. Purpose For patients with hypertension, exercise capacity is reduced by 30%.2 As exercise capacity is a known prognostic marker for adverse cardiovascular outcomes, identifying patients with hypertension with impaired left atrial reservoir strain may also improve cardiovascular risk stratification. With the use of two-dimensional (2D) speckle tracking echocardiography, left atrial strain can now be utilized in the evaluation of left atrial reservoir, conduit, and contractile function. Left atrial strain (LA strain) can now serve as a biomarker of adverse cardiovascular outcomes, including the exercise capacity of patients. Another goal of the study is to identify other clinical and echocardiographic factors that may affect exercise capacity Methods A single center, retrospective cross sectional study was conducted in a tertiary hospital to validate the association of left atrial strain with exercise capacity in terms of metabolic equivalent (METs) achieved during treadmill exercise echocardiography of patients diagnosed with hypertension. The primary objective of this study is to determine the left atrial strain cutoff that reliably discriminates poor, fair, average, good, or high exercise capacity. Data was obtained by conducting a chart and echocardiography review of adult patients from January 2023 to April 2023. The independent association of LA strain with METs was studied with regression analysis. Results were considered significant at p≤0.05 at 95% confidence interval. Receiver-operating characteristic curve analysis was utilized to determine the strength of the LA strain to discriminate between the different exercise capacities. Results A total of 136 patients were included in the study. LA strain, particularly the reservoir, can discriminate exercise capacity, specifically to discriminate good to high capacity from fair to average as their AUC is 0.678 (95% CI 0.58 to 0.77, p=.0001). The best cut-off is 30.2 which resulted to 80% sensitivity (95% CI 66.3 to 90) while specificity is only 51.16% (95% CI 40.1 to 62.1). Spearman rank correlation analysis showed that LA reservoir is significantly correlated with E/A and E/e’. The relationships are linear and positive. Among the other 2D echo parameters, only EDV, E/a and E/e’ were found to have a linear relationship or correlation with METS. Conclusion The study revealed that there is moderate correlation of LA reservoir strain in terms of METS achieved during treadmill stress echocardiography (rs=0.3196, p=0.0001).LA reservoir strain AUCLA strain and other echo parameters

Left atrial strain parameters are able to predict presence of atrial fibrillation

Abstract Background Three-dimensional speckle-tracking echocardiography allows evaluation of left atrial function, left atrial function has been assessed in various diseases for prognostication [1]. Atrial fibrillation (AF) is most common arrhythmia, and one of its manifestations is increased left atrial filling pressure and left atrial dilatation. Methods Echocardiography loops were collected between December 2019 and December 2021, only valid atrial loops, and sinus rhythm during examination. Spearman test was used for correlation matrices of left atrial parameters; uni- , multivariate and binary logistic regression to predict presence or absence of atrial fibrillation. Results A total of 116 patients (50% females) aged 76.9±11.2 were included in the analysis. Males and females differed in anthropometric and other clinical parameters. Intra- and interobserver variability was close to 1% since most of the measurements are semi-automatized. 2D and 3D left atrial volumes correlated significantly (r=0.8, P<0.0001, Fig.1). Almost all left atrial strain measurement uni- and multivariately predicted the presence of atrial fibrillation, binary logistic regression identified two most significant parameters (left atrial longitudinal strain reservoir and conduit phase, LASr, LAScd, P=0.042, P=0.044, respectively, Fig.2). LASr is significantly greater in patients without history of AF vs patient with AF history, (16±16, 10.5±7.1, respectively, P=0.012). The probability of sinus rhythm increases linearly with the increasing value of LASr. Conclusion Left atrial longitudinal strain was able to differentiate patients with paroxysmal atrial fibrillation as compared to patients without history of this arrhythmia.

Differences in left atrial stain, endothelial glycocalyx, arterial elasticity and myocardial efficiency between ESUS, lacunar, cardioembolic and atherosclerotic type of stroke

Abstract Background Patients with stroke are at greater risk of developing cardiovascular complications. Purpose We addressed endothelial glycocalyx, arterial stiffness, left atrial and ventricular function in patients with lacunar, atherosclerotic, cardioembolic and stroke of undetermined source (ESUS). Methods We recruited 194 patients (aged 58.8± 10.8 years old) with acute cerebral stroke (47 lacunar, 50 atherosclerotic,48 ESUS and 49 cardioembolic) and 50 controls with similar risk factors and 40 controls with similar profile regarding common risk factors (diabetes, hypertension, hyperlipidemia, coronary artery disease, smoking; p>0.05 for all comparisons). We measured: (1) perfused boundary region (PBR) of the sublingual microvessels (diameter range 5–25 μm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity carotid-to-femoral (PWV), central systolic blood pressure (cSBP), and central diastolic blood pressure (cDBP), (3) Left atrial (LA) strain using speckle-tracking imaging, (4) left ventricular global longitudinal strain and (5) left ventricular myocardial work index (GWI), constructive work (GCW), wasted work (GWW) and work efficiency (GWE), (6) ventriculoarterial coupling, expressed by the ratio PWV/GLS. Results Compared with controls, patients with stroke had higher PWV (11.98±3.21 vs 9.61±1.28 m/sec, p=0.001), PBR (2.20±0.31 vs 1.94±0.20, p=0.019) and central SBP (137.41±24.83 vs 121.15±17.46 mmHg, p=0.018), while LV ventricular (-16.44±4.70 vs -20.89±2.45%, p=0.001) and atrial deformation (26.81±9.32 vs 37.05±5.08%, p<0.001) were more impaired in patients with stroke (p < 0.05). Patients with ESUS had more impaired LA reservoir strain and contraction strain compared to the other 2 stroke types (ESUS 22.9±8.72%, -13.90±4.96%, Lacunar 29.71±10.52%, -16.11±6.10%, atherosclerotic 26.78±10.14%, -13.74±5.65%, p<0.05). Also, patients with ESUS demonstrated better PBR compared to the lacunar and atherosclerotic types (ESUS 2.10±0.27 μm, Lacunar 2.26±0.29 μm, atherosclerotic 2.19±0.29μm, p<0.05). Patients with atherosclerotic stroke had higher PWV compared with other stroke types (Atherosclerotic: 13.59±3.87 m/sec, Lacunar: 11.41±2.35 m/sec, Cardioembolic: 10.66±3.28 m/sec, ESUS: 11.72±2.67 m/sec). Also, patients with atherosclerotic stroke demonstrated the worst PWV/GLS ratio (Atherosclerotic: -0.97±0.35, Lacunar: -0.69±0.25, Cardioembolic: -0.76±0.21, ESUS: -0.70±0.28). Patients with cardioembolic stroke showed similar trend with ESUS, as far LA strain is considered. Conclusion Patients with stroke have impaired atrial strain, endothelial glycocalyx and arterial stiffness, compared with controls. Arterial stiffness and ventriculoarterial coupling are more affected in atherosclerotic strokes. LA strain is more impaired in the ESUS and cardioembolic stroke albeit that endocalyx, though abnormal,is less impaired in these stroke types.

Left atrial reservoir strain measured by three-dimensional echocardiography is associated with major adverse cardiovascular events in the general population

Abstract Background Left atrial (LA) strain measured by three-dimensional (3D) echocardiography (3DE) is a novel way of evaluating LA function. The prognostic value of LA strain by 3DE in incident heart failure (HF) and cardiovascular (CV) death has not previously been documented. Purpose We south to investigate whether 3D LA strain measures were associated with incident heart failure (HF) and cardiovascular (CV) death in a population at low risk of CV events. Methods A total of 1,934 participants from a prospective longitudinal cohort study of the general population underwent a comprehensive transthoracic echocardiographic examination including 3DE where LA reservoir strain (LASr), conduit strain (LAScd) and contraction strain (LASct) were quantified. All participants were at sinus-rhythm during 3DE. The endpoint was a composite of HF and CV death. Cox proportional hazards regression was applied. Multivariable adjustments were made for the ARIC-HF risk score (age, gender, heart rate, systolic blood pressure, antihypertensive medication, diabetes, ischemic heart disease, smoking, and body mass index) and left atrial volume index. Results Mean age was 54±17 years, 43% were male. During a median follow-up time of 4.8 years (interquartile range 4.3-5.4 years), 89 participants (4.6%) either developed HF or died of a CV cause. In univariable analysis, LASr and LAScd, but not LASct were significantly associated with the outcome, but after multivariable adjustment only LASr remained significantly associated with outcome (HR 1.04 (95% CI: 1.01-1.08), p=0.016, per 1% decrease) while LAScd and LASct did not. LASr provided incremental prognostic information beyond the ARIC-HF risk score (continuous NRI 0.21±0.11, p=0.027). Compared to participants with a LASr in the 1st tertile (LASr>32%) Participants with an LASr in the in the 3rd tertile (LASr<26.5%) had an almost 7-fold increased risk of HF or CV-death (HR 6.93 (95% CI 3.29-14.58; p=0.001)(Figure). Conclusion LA reservoir strain assessed by 3DE was independently associated with incident HF and CV death, which was not the case for LA conduit and contraction strain. In addition, LA reservoir strain added incremental value beyond clinical risk scores.

Left atrial strain is associated with cardiovascular outcomes in children with congenitally corrected transposition of the great arteries

Abstract Background The assessment of the systemic right ventricular (sRV) function in congenitally corrected transposition of the great arteries (ccTGA) by echocardiography is restricted by its complex geometry. Purpose To determine the utility of left atrial strain (LAS) and sRV longitudinal strain (sRV-LS) in the prediction of outcomes in children with ccTGA. Methods This nested case-control study included all patients <21 years old with unrepaired ccTGA at our tertiary pediatric institution who had an echocardiogram prior to cardiovascular outcomes (milrinone-dependent heart failure, ventricular assistant device, heart transplant or death). LAS (both R wave and P wave references) and sRV-LS were measured using TomTec AutoStrain. To account for potential confounders, cases and controls were matched (1 cases vs 3 controls) by age ± 1 year and tricuspid regurgitation (TR) severity (none/mild vs. moderate/severe). Univariable conditional logistic regression was employed to assess the association between LAS and sRV-LS with outcomes among matched patients. Results Of 101 patients (64% male) with echocardiogram performed at 1.78 years old (IQR 0.02, 9.80), 14 (14%) developed an outcome. Baseline characteristics, LAS, and sRV-LS are depicted in Table 1. LAS and sRV-LS were not discriminative between age-matched cases and controls. In the matched cases and controls for TR severity, each unit-increase in LAS conduit phase (LAScd R and LAScd P) was associated with 18% and 22% higher odds of outcomes respectively, although these did not achieve statistical significance (LAScd R OR 1.2, 95% CI 1.0-1.4, p=0.09; LAScd P OR 1.2, 95% CI 1.0-1.5, p=0.08, Table 2). Conclusions After controlling for TR severity as a potential confounding factor, the conduit phase of LAS by both R wave and P wave references may have clinical implications as predictors of cardiovascular outcomes in patients with ccTGA. Larger and more well-powered studies are needed to further evaluate this association and studying longitudinal changes in LAS may provide insight in the development of outcomes in this population.

Unveiling a hide side of the athlete's heart: a CMR focus on the left atrium.

Abstract Background cardiac magnetic resonance (CMR) is the gold standard to evaluate cardiac chambers’ dimensions and function, but data on left atrium (LA) dimensions and function among elite athletes are lacking. Objective to describe LA size and function among a cohort of elite athletes and evaluate eventual differences based on sports discipline and gender. Methods We enrolled 120 Olympic athletes with un-remarkable cardiovascular pre-participation screening tests (mean age 25±5 years, 50% males, 25% skill, 25% power, 25% mixed, 25% endurance). All the athletes underwent CMR without contrast administration. LA dimensions, in terms of absolute and indexed area and volume, were computed using 4- and 2-chamber steady state precession cine-sequences. LA ejection fraction (LAEF) and LA coupling index (LACI index, as the ratio between LA and LV end-diastolic volumes) were calculated. Cine-images were also used to analyse atrial deformation with a dedicated offline software to measure LA global longitudinal strain. LA dimensions and function were compared between males and females and athletes of different sports categories based on European classification. Results Among the entire cohort, endurance athletes showed the greatest remodelling in terms of LA and LV dimensions (Table). There were no significant differences in LAEF and LV-EF between athletes of different sport categories (p=0.121 and p=0.679). A trend in increasing LA volumes and decreasing LA strain consistent with a growing cardiovascular demand was observed, but the only statistically significant difference was between skill athletes and all the other groups for LA volumes (p<0.001), while there were no significant differences in LA strain (p=0.170). LACI did not differ between athletes of different sports categories (p=0.170). Female athletes showed higher LAEF and LA strain than males (respectively 55±5 vs 52±6% p=0.012 and 35±7 vs 32±7%, p=0.009) while LACI did not differ based on gender (19±5% for both females and males, p=0.385). Conclusion Among our cohort of Olympics, LA remodelling was observed in all athletes, being less evident in skill group, as for the LV. Thus, the ratio between LA and LV did not differ between sport categories. LAEF and LA strain were not significantly different between athletes of different sports categories although LA strain was slightly lower in endurance. Female athletes showed higher LAEF and LA strain than males, while LACI was not different based on gender.

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

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

Left atrial strain differences between hypertensive and sarcomeric left ventricular hypertrophy: a sign of sarcomeric auricular myopathy?

Abstract Introduction In clinical practice, left ventricular (LV) hypertrophy is a common finding that can be caused by physiologic or pathologic conditions. An etiologic diagnosis is extremely important because it may change the prognosis and management of the patient and his family. Left atrial (LA) dysfunction is common due to diastolic dysfunction but, in patients with sarcomeric LV hypertrophy, primary cardiomyopathy disease could also be present. Purpose To evaluate if there are differences in LA function between arterial hypertension (HT) and hypertrophic cardiomyopathy (HCM) patients. Methods 73 patients with HCM (according to ESC guidelines criteria) and 82 patients with HT (under treatment with ≥1 hypertensive drug for ≥3 months) and ≥13mm of LV hypertrophy underwent an echocardiography to assess LA function with strain analysis and LV diastolic function. Continuous normally distributed variables were compared with T-student test and categoric variables with square-chi or exact Fisher test if required, accepting as significant a p-value <0.05. Results Globally, HCM patients showed thicker LV walls and larger LA indexed volumes (18.7±4.7 vs. 13.3±0,8 mm and 44.9±20.7 vs. 30.7±8.8 ml/m2, p<0.000 for both). Also, HCM patients presented diastolic dysfunction and atrial fibrillation history in a higher frequency (31 vs. 7.6% and 16.4% vs. 0%, p<0.000 for both). LA strain was significantly lower in HCM patients as compared to the HT group (LA contractile 11.5±5.8 vs. 17.2±4.4, p<0.000; LA conduit 12.2±5.4 vs. 13.3±3.8, p=0.041; and LA reservoir 23.9±8.7 vs. 31.1±5.9, p<0.000). In the subgroup of patients with moderate-severe LV hypertrophy (<17mm) and no significant mitral regurgitation (n=103; HCM=21, HT=82), LA contractile strain remained lower in HCM as compared to HT patients (13.2±4.8% vs. 17.2±4.4%, p<0.000) (figure 1); without differences in diastolic dysfunction, LA volumes, significant mitral regurgitation or atrial fibrillation history. Conclusions Our results show that LA strain is more impaired in HCM patients as compared to HT patients. Specifically, contractile LA strain remained lower even in those patients with moderate-severe LV hypertrophy, despite having similar LV diastolic function, LA indexed volumes, significant mitral regurgitation, or atrial fibrillation history. These findings could be caused by HCM involvement of the LA myocytes. In the context of moderate-severe hypertrophy of unknown origin with non-significant mitral regurgitation, the detection of abnormally reduced LA strain could indicate the presence of an HCM.Figure 1

Left atrial reservoir strain differentiates cardiac amyloidosis and hypertrophic cardiomyopathy

Abstract Aims Availability of mortality-reducing therapies for cardiac amyloidosis (CA) has led to an increase in referral rates to tertiary care centers. Investigations to improve diagnosis rates are urgently needed, as diagnosis of CA requires a multimodal approach and its early diagnosis is crucial due to high mortality in untreated patients. The aim of this study is to evaluate the accuracy of the left atrial reservoir strain (LASr) in differentiating CA patients from patients with hypertrophic cardiomyopathy (HCM). Methods This is a cross-sectional analysis from the Graz HCM Registry, a prospective single-center cohort study enrolling consecutive patients with a HCM phenotype. This analysis included HCM and CA patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses in 100 HCM and 95 CA patients. Results Compared to HCM patients, CA patients were more frequently male [79 (83%) vs. 54 (54%); p<0.001] and older [78 (73-81) vs. 58 (47-70) years; p<0.001]. Moreover, CA patients had a lower BMI [25.0 (22.8-26.9) vs. 26.5 (24.3-29.7) kg/m²; p=0.002] as well as lower systolic [134±20 vs. 142±25 mmHg; p=0.018] and diastolic blood pressure [78±12 vs. 84±12 mmHg; p<0.001]. Additionally, CA patients had higher NT-proBNP [2533.0 (1146.0-5016.0) vs. 543.0 (195.0-1381.0) pg/ml; p<0.001] and lower eGFR [58.4±19.1 vs. 80.1±22.2 ml/min/1.73m²; p<0.001]. LASr was significantly worse in CA patients compared to HCM patients [9.2 (5.6-13.0) vs. 21.7 (14.8-27.6) %; p<0.001]. Multivariable logistic regression analysis revealed LASr as an independent predictor of CA [OR=0.936 (95% CI 0.877-0.998)], adjusting for covariates. ROC analysis showed an AUC of 0.80 (95% CI 0.73-0.86) for LASr to discriminate CA from HCM. LASr ≤14.3% demonstrated a 80% sensitivity and 79% specificity for the identification of CA patients. Sensitivity analyses involving 74 sex- and age-matched patients yielded materially unchanged results. Conclusion Compared to HCM patients, LASr was diminished in CA patients and an independent predictor of CA. Moreover, LASr showed high diagnostic accuracy in differentiating CA and HCM patients. Prospective studies are needed to evaluate the added value of left atrial strain in the diagnostic work-up of CA patients.ROC curve of LASr

Left atrial longitudinal strain behavior in patients with cryptogenic stroke - a case control study

Abstract Background A significant percentage of ischemic strokes classified as cryptogenic stroke (CS) where the definition is varied according to the type of classification used. Left atrial (LA) function has a role in determining the possible cardio-embolic source of stroke. Using speckle tracking transthoracic echocardiography (TTE) we can detect the early changes in left atrial function by measuring left atrial longitudinal strain (LALS). Aim To evaluate the left atrial stain in patients with a cryptogenic stroke as compared to a healthy papulation. Method and results We recruited 50 cryptogenic ischemic stroke patients with mean age of 44.7 years and 50 % were male who treated consecutively as for first CS, and 50 age-and sex-matched healthy stroke-free controls. Using Speckle tracking TTE analysis we measured the global , passive and active longitudinal LA strain corresponding to the reservoir (LASRES), conduit(LASCD), and contractile function(LASCT),respectively in addition to standard other LA parameters and filling pressure parameters of Left ventricle(LV) in both group. Data were compared using t-test and Mann-Whitney test. Cryptogenic stroke patients as compared with controls had significantly reduced value of all components of LALS [Mean value of LASRES, LASCD and LASCT in CS group versus control group were 25.15±6.79 versus 43.95±4.62 (P-value <0.01), 14.41±3.53 versus 25.68±3.30 (P- value <0.01), 10.73±3.35 versus 18.28±1.60 (P-value <0.01) respectively] (Figure 1 and Figure 2). There were no significant differences in means of LA area and LA volume index in both groups (P value >0.05). Between parameters of LV filling pressures, it was noticed that early diastolic transmitral flow velocity (E) and early diastolic velocity at annulus (E’) were statistically lower in CS patients as compared to control group (P-value <0.01). In addition, the Cluster and Discriminant analysis used confirmed that LASRES, LASCD and LASCT were significantly lower in value in cryptogenic stroke patients in comparison to Control group which can be used to detect early LA dysfunction. Conclusion LA longitudinal strain in all components were significantly impaired in patients with CS. Measuring LALS parameters can be useful in determining early LA dysfunction in cryptogenic stroke patients.Figure 1-left atrial strain components.Figure 2 -left atrial strain component.

Characterization of left atrial function during cardiac (reverse) remodeling induced by pregnancy

Abstract Introduction The hemodynamic overload in pregnancy leads to cardiovascular remodeling, characterized by enlargement of left atrial (LA) and ventricular (LV) volumes associated with impaired LV relaxation, maintaining preserved systolic function. These changes are reversible during postpartum. Few scientific evidence has been published about LA function yet. Purpose To assess the changes in LA function through two-dimensional speckle tracking echocardiography analysis during pregnancy and its recovery up to 1 year after delivery and to determine potential predictors of its progression. Methods This prospective cohort study included volunteer pregnant women (healthy, obese and/or hypertensive and/or with gestational diabetes) recruited in two tertiary centers between 2019 and 2021. Women were evaluated by transthoracic echocardiography at the 1st trimester [1T, 10-15 weeks, baseline], 3rd trimester [3T, 30-35 weeks, peak of cardiac remodeling] of pregnancy as well as at the 1st, 6th and 12th month after delivery (during RR). Generalized linear mixed-effects models evaluated the extent of RR, including the variation of left atrial strain and its potential predictors. Results We included 130 pregnant women with a median age of 33 [30,36] years, 39,2% multiparas. Fifty-four (41.5%) were diagnosed with at least one cardiovascular risk factor. A significant enlargement of LA volume (24 [22, 28]mL/m2 to 29 [25, 33]mL/m2, p<0.001) associated with the increase of E/e’ (5.85 [5.08, 6.36] to 6.70 [5.67, 7.82], p<0.001) was observed from 1T to 3T, both recovering as soon as 1 month after delivery (LA volume: 29 [25, 33]mL/m2 to 24 [20, 27] mL/m2, p<0.001; E/e’: 6.70 [5.67, 7.82] to 5.70 [4.82, 6.47], p<0.001). Regarding LA function, a significant reduction of LA strain was verified from 1T to 3T (35 [31, 41]% to 31 [29, 36]%, p<0.001), recovering 6 months postpartum (31 [29, 36]% to 33 [30, 38]%, p=0.035). Systemic vascular resistance seemed to be an independent predictor of lower LA strain (-3.83 [-6.40, -1.25], p=0.004). The presence of cardiovascular risk factors (-0.80 [-2.28, 0.68], p=0.287), smoking habits (-1.26 [-2.82, 0.30], p=0.112), parity (-0.33 [-1.93, 1.27], p=0.684) and age (-0.11 [-0.29, 0.08], p=0.257) showed a non-significant impact in LA strain. Conclusion Despite the recovery in diastolic function and LA volume 1 month after delivery, the LA function only significantly improved 6 months later. Systemic vascular resistance was revealed as an independent predictor of LA strain.

Left atrial remodeling and novel biomarkers in obese patients with heart failure with preserved ejection fraction compared to type-2-diabetics and obese controls: a cardiac magnetic resonance study

Abstract Background Elevated filling pressures and subsequent left atrial (LA) dilation are common findings in heart failure with preserved ejection fraction (HFpEF), reflecting a chronic state of the disease and holding prognostic value. HFpEF is thought to develop through a long-term pro-inflammatory state triggered by comorbidities, such as obesity and type 2 diabetes mellitus (T2DM). Emerging biomarkers have shown associations with structural remodeling, but also increased myocardial stiffness. Purpose To elucidate the relationship between LA volume and function, and prognostic biomarkers (NT-proBNP, BNP-32, IL1R1, Galectin-3, and Pentraxin-3) in an obese cohort with T2DM or HFpEF and T2DM, versus healthy obese controls. Methods We conducted a prospective cohort study of 35 obese participants, divided into three groups: T2DM (n=16), HFpEF with T2DM (NYHA II-III, n=13), and healthy obese controls (n=6). Each subject underwent comprehensive CMR at a 3T scanner to assess LA strain and volume. Atrial strain was assessed on 2- and 4-chamber view cine images by experienced CMR investigators using dedicated software. Routine labs and serum levels of biomarkers were measured. If labs or images were repeated, the average was calculated. Statistical significance was determined through ANOVA and student’s t-test for group comparisons and Pearson correlation for associations between LA parameters and biomarker levels. Results Cohorts were evenly matched in terms of demographics, vital signs, and ventricular volumes and functions, as depicted in Table 1. Only one patient in the HFpEF subgroup reported history of atrial fibrillation. Both minimum and maximum LA volumes were significantly elevated in the HFpEF group compared to the T2DM and control groups (p < 0.018). LA strain (conduit, reservoir, and booster) was notably compromised in the HFpEF cohort, contrasting with the obese T2DM group where LA strain values did not differ significantly from those observed in obese controls (Figure 1). Biomarker analysis revealed a marked increase of NT-proBNP, BNP-32, Galectin-3, and Pentraxin-3 in the HFpEF cohort. In the HFpEF cohort, IL1R1 was the only biomarker that was strongly associated with higher left ventricular enddiastolic (r=0.69, p=0.003) and endsystolic volumes (r=0.75, p=0.009). Moreover, IL1R1 was the only biomarker associated with atrial functional changes (booster strain, r=-0.57, p=0.043) in the HFpEF patients. Our findings indicate that ILR1 plays a crucial role in the cardiometabolic (obesity-T2DM) HFpEF phenotype, with its activation leading to advanced cardiac remodeling. Conclusion Obese HFpEF patients with T2DM showed severely altered left atrial morphology and function compared to those that are only obese or obese with T2DM. Moreover, our findings revealed that atrial remodeling in this population is driven by pro-fibrotic inflammatory pathways.Characteristics of the study cohortLeft atrial strain analysis

Echocardiographic signs of atrial cardiopathy and MRI-detected silent brain infarcts in a middle-aged cohort: the Akershus Cardiac Examination 1950 Study

Abstract Background Atrial fibrillation (AF) is linked to clinical stroke and silent brain infarction (SBI). In the majority of AF patients, there exists a recognized form of atrial cardiopathy, and it is suggested that atrial cardiopathy, even in the absence of AF, may serve as a risk factor for stroke. However, existing evidence is limited, and it remains unclear whether atrial cardiopathy indeed poses a risk for stroke and SBI. Purpose We aimed to investigate the association between echocardiographic signs of atrial cardiopathy and the detection of SBI through magnetic resonance imaging (MRI) in a middle-aged cohort from the general population. Methods In the prospective Akershus Cardiac Examination (ACE) 1950 Study conducted within the general population in Norway, cardiovascular risk assessment including transthoracic echocardiography, was undertaken at study inclusion between 2012 and 2015. We assessed body surface area-indexed left atrial (LA) maximum and minimum volume, as well as LA reservoir and contractile strain. Subsequently, brain MRI was conducted in a subset of the cohort between 2017 and 2023. SBI was defined as presence of neuroimaging sign of infarcts, including lacunes, in individuals without a history of stroke. Logistic regression analyses were performed to explore the associations between echocardiographic measures of atrial cardiopathy and SBI on MRI, adjusting for sex, age, hypertension, and diabetes. Results A total of 397 out of 3706 (10.7%) participants in the ACE 1950 study underwent MRI examination and were included in this analysis. At the time of MRI, the mean age was 70.0±2.2 years, with 157 (40%) women, 248 (62%) with hypertension, and 36 (9%) with diabetes at study inclusion. SBI was present in 51 (13%), of which only 1 (2%) had known AF. After excluding 18 participants with pre-existing AF, no significant difference were observed in LA volumes or LA strain between participants with or without SBI (Figure 1). In unadjusted and adjusted logistic regression analyses, neither LA volume nor LA strain were associated with SBI (Table 1). Conclusion Echocardiographic signs of atrial cardiopathy were not associated with silent brain infarcts in a middle-aged cohort from the general population.

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

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

Head to head comparison of left atrial and ventricular strain at rest in prediction of exercise induced elevated left ventricular filling pressure

Abstract Background Both left atrial (LA) and ventricular (LV) strain at rest have been reported as predictors of exercise induced elevated LV filling pressure. However, head to head comparison of LA and LV strain is very limited. The purpose of this study was to compare peak atrial longitudinal stain (PALS) and LV global longitudinal strain (GLS) in prediction of exercise induced elevated LV filling pressure. Methods From January 2018 to December 2022, 286 consecutive patients underwent treadmill stress echocardiography. Patients with atrial fibrillation, E/e’ ≥ 15 at rest, and LV ejection fraction < 50% were excluded from the study, and 217 patients were recruited. All patients underwent routine echocardiography including PALS and GLS measurements. Exercise induced elevated LV filling pressure was defined as post-exercise septal E/e’ ≥ 15. Results Both PALS and GLS were obtained in 212 patients, and 50 patients had post-exercise E/e’ ≥ 15. Receiver oriented curve analysis revealed best cutoff value of 23.9% for PALS (sensitivity 68%, specificity 67%, respectively) and -17.7% for GLS (sensitivity 84%, specificity 65%, respectively) in prediction of post-exercise E/e' ≥15. Univariate logistic analysis demonstrated that impaired PALS, impaired GLS and raised E/e’ at rest were associated with post-exercise E/e’ ≥ 15. However, multivariate logistic analysis revealed that GLS and E/e’ were independent predictors of post-exercise E/e’ ≥ 15, but PALS was not. Conclusions Both impaired PALS and GLS at rest can predict post-exercise E/e’ ≥ 15.0. However, multivariate logistic analysis has demonstrated that impaired GLS, not PALS was independent predictor of exercise induced elevated LV filling pressure.

The impact of preoperative four-chamber strain on failure of the maze IV procedure for atrial fibrillation: insights from conventional and speckle-tracking echocardiography

Abstract Background Prior studies have linked decreased left atrial (LA) and left ventricular (LV) function to the failure of both catheter ablation and surgery for atrial fibrillation (AF). Yet, the effects of right atrial (RA) and right ventricular (RV) function on the failure of interventional therapy remain unexplored. This study evaluates four-chamber strain parameters using conventional echocardiography and speckle-tracking analysis to evaluate the contributions of preoperative left heart and right heart function to the failure of surgery for atrial fibrillation. Methods We retrospectively analyzed 821 patients who had surgical AF ablation, using pre- and postoperative data from electronic records to assess AF recurrence and thromboembolic events. Of these, 531 had LA ablation only and 290 had bi-atrial Maze-IV procedures. Four-chamber strain was evaluated via speckle-tracking on preoperative echos with TomTec Arena, excluding low-quality images. Univariate and multivariate logistic regression analyses were conducted to assess the influence of AF duration, LV ejection fraction, age, and gender on post-PAF surgery AF recurrence, thromboembolic events with results shown as odds ratios (ORs) in the table. An OR over 1.00 indicates a higher recurrence risk per variable increment. SAS software was used for all statistical analysis. Results In our cohort with a median age of 67.4±11.0 (46.2% female), unadjusted analyses revealed that increased LA and RA volumes and decreased RV free wall strain were significantly associated with AF recurrence post-surgical ablation. Conversely, each unit decrease in LA and RA peak reservoir strain corresponded to a 6% increase in the risk of AF recurrence, indicating an inverse relationship. Adjusted analyses for LA and RA end diastolic volumes and strain values showed a similar direction of association with AF recurrence, though these were not statistically significant. Similarly, lower LA and RA peak strains and larger atrial volumes were suggestive of an increased risk for postoperative thromboembolic stroke, but did not reach statistical significance, potentially due to the low event rate (1.8% of the cohort). Conclusion Conventional echocardiography offers a practical tool for identifying patients at high risk for AF recurrence and potential thromboembolic events after AF ablation surgery. Our study confirms that reduced preoperative LA, RA and RV strain values and enlarged volumes of LA and RA are strongly associated with AF recurrence following surgical ablation. Additionally, RA strain and volume are as predictive as LA metrics, underscoring their importance in risk stratification. These echocardiographic parameters may also hold value in forecasting the likelihood of postoperative stroke.

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.