3D echocardiographic reference ranges for normal left ventricular volumes and strain: Results fromthe EACVI NORRE study

Aim To obtain the normal ranges for 3D echocardiography (3DE) measurement of left ventricular (LV) volumes, function, and strain from a large group of healthy volunteers. Methods and results A total of 440 (mean age: 45613 years) out of the 734 healthy subjects enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study had good-quality 3DE data sets that have been analysed with a vendor-independent software package allowing homogeneous measurements regardless of the echocardiographic machine used to acquire the data sets. Upper limits of LV end-diastolic and end-systolic volumes were larger in men (97 and 42 mL/m2) than in women (82 and 35 mL/m2; P<0.0001). Conversely, lower limits of LV ejection fraction were higher in women than in men (51% vs. 50%; P<0.01). Similarly, all strain components were higher in women than in men. Lower range was -18.6% in men and -19.5% in women for 3D longitudinal strain, -27.0% and -27.6% for 3D circumferential strain, -33.2% and -34.4% for 3D tangential strain and 38.8% and 40.7% for 3D radial strain, respectively. LV volumes decreased with age in both genders (P<0.0001), whereas LV ejection fraction increased with age only in men. Among 3DE LV strain components, the only one, which did not change with age was longitudinal strain. Conclusion The NORRE study provides applicable 3D echocardiographic reference ranges for LV function assessment. Our data highlight the importance of age- and gender-specific reference values for both LV volumes and strain. All rights reserved

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant–neutralizing antibody that is a strong candidate for clinical development

Quantification of the relative contribution of the different right ventricular wall motion components to right ventricular ejection fraction

Abstract Three major mechanisms contribute to right ventricular (RV) pump function: (i) shortening of the longitudinal axis with traction of the tricuspid annulus towards the apex; (ii) inward movement of the RV free wall; (iii) bulging of the interventricular septum into the RV and stretching the free wall over the septum. The relative contribution of the aforementioned mechanisms to RV pump function may change in different pathological conditions. Our aim was to develop a custom method to separately assess the extent of longitudinal, radial and anteroposterior displacement of the RV walls and to quantify their relative contribution to global RV ejection fraction using 3D data sets obtained by echocardiography. Accordingly, we decomposed the movement of the exported RV beutel wall in a vertex based manner. The volumes of the beutels accounting for the RV wall motion in only one direction (either longitudinal, radial, or anteroposterior) were calculated at each time frame using the signed tetrahedron method. Then, the relative contribution of the RV wall motion along the three different directions to global RV ejection fraction was calculated either as the ratio of the given direction’s ejection fraction to global ejection fraction and as the frame-by-frame RV volume change (∆V/∆t) along the three motion directions. The ReVISION (Right VentrIcular Separate wall motIon quantificatiON) method may contribute to a better understanding of the pathophysiology of RV mechanical adaptations to different loading conditions and diseases

Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease

A novel software tool to semi-automatically characterize tricuspid valve function and shape using trans-thoracic 3D echocardiography

none8noneVeronesi, F.; Muraru, D.; Addetia, K.; Corsi, C.; Lamberti, C.; Lang, R.M.; Mor-Avi, V.; Badano, L.P.Veronesi, F.; Muraru, D.; Addetia, K.; Corsi, C.; Lamberti, C.; Lang, R.M.; Mor-Avi, V.; Badano, L.P

Artificial intelligence based left ventricular ejection fraction and global longitudinal strain in cardiac amyloidosis

Background: Assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) plays a key role in the diagnosis of cardiac amyloidosis (CA). However, manual measurements are time consuming and prone to variability. We aimed to assess whether fully automated artificial intelligence (AI) calculation of LVEF and GLS provide similar estimates and can identify abnormalities in agreement with conventional manual methods, in patients with pre-clinical and clinical CA. Methods: We identified 51 patients (age 80±10 years, 53% male) with confirmed CA according to guidelines, who underwent echocardiography before and/or at the time of CA diagnosis (median (IQR) time between observations 3.87 (1.93, 5.44) yrs). LVEF and GLS were quantified from the apical 2- and 4-chamber views using both manual and fully automated methods (EchoGo Core 2.0, Ultromics). Inter-technique agreement was assessed using linear regression and Bland-Altman analyses and two-way ANOVA. The diagnostic accuracy and time for detecting abnormalities (defined as LVEF ≤50% and GLS≥-15.1%, respectively) using AI was assessed by comparisons to manual measurements as a reference. Results: There were no significant differences in manual and automated LVEF and GLS values in either pre-CA (p=0.791 and p=0.105, respectively) or at diagnosis (p=0.463 and p=0.722). The two methods showed strong correlation on both the pre-CA (r=0.78 and r=0.83) and CA echoes (r=0.74 and r=0.80) for LVEF and GLS, respectively. The sensitivity and specificity of AI-derived indices for detecting abnormal LVEF were 83% and 86%, respectively, in the pre-CA echo and 70% and 79% at CA diagnosis. The sensitivity and specificity of AI-derived indices for detecting abnormal GLS was 82% and 86% in the pre-CA echo and 100% and 67% at the time of CA diagnosis. There was no significant difference in the relationship between LVEF (p=0.99) and GLS (p=0.19) and time to abnormality between the two methods. Conclusion: Fully automated AI-calculated LVEF and GLS are comparable to manual measurements in patients pre-CA and at the time of CA diagnosis. The widespread implementation of automated LVEF and GLS may allow for more rapid assessment in different disease states with comparable accuracy and reproducibility to manual methods

Dynamic three-dimensional evaluation of tricuspid valve morphology and function in patients with pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a common cause of tricuspid valve (TV) dilatation. Because of the impact of PAH on the right ventricle (RV), in-depth understanding of TV morphology and function is important. Methods: Novel custom software was used to trace and measure TV annulus (TVA) in 10 patients with PH and 10 control subjects (CTRL). To trace the TVA, points were selected in rotated planes and then interpolated. TVA was automatically tracked throughout cardiac cycle. Commissures were identified and used to divide the TVA into three segments. After initialization of the coaptation the TV leaflets were identified. The following parameters were automatically computed in 3D throughout the cardiac cycle: annular area, height, eccentricity and displacement, as well as intercommissural segment lengths. Results: Compared to CTRL, in patients with PAH, TVA was larger. The TA was also more circular and with less longitudinal displacement. Changes in annular remodeling were not uniform. The anterior and posterior segments were enlarged, while the septal remained unchanged, probably because the septal leaflet is fixed between the fibrous trigones. Conclusions: This novel software revealed that PAH affects size, shape and function of the TVA, suggesting that 3D analysis may be useful for evaluation of different RV disease states

Dynamic Analysis of the Normal Tricuspid Annulus Using 3D Echocardiography

Purpose: Changes in the geometry of the normal tricuspid annulus (TA) throughout the cardiac cycle, as assessed by three-dimensional transthoracic echocardiography (3DTTE), have not been extensively described. The goal of this study was to characterize normal TA dynamics as a basis for a better understanding of tricuspid valve (TV) pathology. Methods:Westudied 98 subjects (45+15 years, range 19-80 years, BSA 1.81+0.22m2, 44 men) with normal TV who underwent 3DTTE full volume imaging of the right ventricle (RV) from the apical 4-chamber view (Philips, iE33 and GE Vivid E9) at 2 University Hospitals. All study subjects had a normal 2DTTE study, RV systolic pressure ≤35 mmHg and RV ejection fraction ¼ 55+7% (TomTec 4D RV software). Measurements were made (QLAB 9.0, Philips and EchoPAC BT 12, GE) of the TA area, antero-posterior (AP) and septal-lateral (SL) TA dimensions at the onset of systole (closure of the TV), endsystole (prior to TV opening), mid-systole (mid-point between onset and end-systole), early-diastole (initial TV leaflet opening) and late-diastole (TV opening after atrial contraction). Results:MeanTAareaanddimensions varied throughout the cardiac cycle (Table), being the largest in late-diastole and smallest at the onset of systole. TA fractional area change was38%.TAAPdimensionwaslarger than theSLdimension throughout the cardiac cycle (fig.A). Fractional changes in AP and SL dimensions were 23% and 18%, respectively. No significant differences were noted between genders (fig.B) or age groups. Conclusions:NormalTAis ahighly dynamicstructure andthis has important implications for its sizing. Customized software to characterize TA remodeling and dynamics throughout the entire cardiac cycle is needed for a better understanding of TV pathology

Dynamic Analysis of the Normal Tricuspid Annulus Using 3D Echocardiography

Purpose: Changes in the geometry of the normal tricuspid annulus (TA) throughout the cardiac cycle, as assessed by three-dimensional transthoracic echocardiography (3DTTE), have not been extensively described. The goal of this study was to characterize normal TA dynamics as a basis for a better understanding of tricuspid valve (TV) pathology. Methods:Westudied 98 subjects (45+15 years, range 19-80 years, BSA 1.81+0.22m2, 44 men) with normal TV who underwent 3DTTE full volume imaging of the right ventricle (RV) from the apical 4-chamber view (Philips, iE33 and GE Vivid E9) at 2 University Hospitals. All study subjects had a normal 2DTTE study, RV systolic pressure ≤35 mmHg and RV ejection fraction ¼ 55+7% (TomTec 4D RV software). Measurements were made (QLAB 9.0, Philips and EchoPAC BT 12, GE) of the TA area, antero-posterior (AP) and septal-lateral (SL) TA dimensions at the onset of systole (closure of the TV), endsystole (prior to TV opening), mid-systole (mid-point between onset and end-systole), early-diastole (initial TV leaflet opening) and late-diastole (TV opening after atrial contraction). Results:MeanTAareaanddimensions varied throughout the cardiac cycle (Table), being the largest in late-diastole and smallest at the onset of systole. TA fractional area change was38%.TAAPdimensionwaslarger than theSLdimension throughout the cardiac cycle (fig.A). Fractional changes in AP and SL dimensions were 23% and 18%, respectively. No significant differences were noted between genders (fig.B) or age groups. Conclusions:NormalTAis ahighly dynamicstructure andthis has important implications for its sizing. Customized software to characterize TA remodeling and dynamics throughout the entire cardiac cycle is needed for a better understanding of TV pathology