AIMS:Skeletal muscle energetic augmentation might be a mechanism via which intravenous iron improves symptoms in heart failure, but no direct measurement of intrinsic mitochondrial function has been performed to support this notion. This molecular substudy of the FERRIC-HF II trial tested the hypothesis that ferric derisomaltose (FDI) would improve electron transport chain activity, given its high dependence on iron-sulfur clusters which facilitate electron transfer during oxidative phosphorylation. METHODS AND RESULTS:Vastus lateralis skeletal muscle biopsies were taken before and 2 weeks after randomization. Mitochondrial complex I, II, and I&II respiration were quantified with respirometry of permeabilized fresh skeletal muscle biopsies. Net respiratory capacities, reflecting respiration that is truly available for adenosine triphosphate generation, were calculated by subtracting non-phosphorylating LEAK respiration. Complex I-V and myoglobin protein levels, and skeletal muscle fibre type composition were assayed. Patients randomised to FDI (n = 21) or placebo (n = 19) were similar (age 66 ± 13 years, 73% men, left ventricular ejection fraction 37 ± 8%, 48% New York Heart Association class III, 50% diabetic). After 2 weeks, total complex I-linked respiration (0.33 [interquartile range 0.24-0.37] vs. 0.19 [0.06-0.27] nmol/min/mg, p = 0.03) and net complex I-linked respiration (0.21 [0.16-0.24] vs. 0.11 [0.04-0.16] nmol/min/mg, p = 0.01) were higher in patients allocated to FDI. There was no intergroup difference in other respiratory states, in mitochondrial abundance as reflected by complex I-V protein levels, and in skeletal muscle myoglobin and oxidative fibre type content. CONCLUSIONS:Iron repletion induces an early, selective, and potentially direct enhancement of mitochondrial complex I-dependent respiration in the skeletal muscle of heart failure patients. This could be harnessed to optimize repletion protocols to maximize patient benefits.

Background: Studies utilising invasive pressure‒volume loops offer valuable insights into left ventricular (LV) contractility, yet their availability remains limited. Conversely, noninvasive indices are accessible and reproducible; however, their validation in patients with aortic stenosis (AS) is lacking. We sought to validate the noninvasive indices of PVL studies in a group of symptomatic severe AS patients. We recruited patients with symptomatic severe AS admitted for transcatheter aortic valve implantation (TAVI) for invasive PVL studies. Noninvasive PVL indices were measured with three-dimensional (3D) echocardiography with a prespecified protocol. The agreement between invasive and noninvasive calculation methods was assessed. Results: Eleven patients (11) were recruited for this pilot study. The noninvasive end-systolic pressure‒volume relationship (ESPVR) determined by Kelly's method (Ees(sb) = 0.9 × systolic blood pressure/end-systolic volume (ESV)) had the best agreement with the invasive ESPVR (limits of agreement -1.7 to 2.1 with a percentage error of 24%, one sample T test p =0.504). Systolic blood pressure, as measured by the brachial blood pressure cuff, had the best agreement with end-systolic pressure in severe aortic stenosis (limits of agreement -60 to 60 with a percentage error of 3%, one sample T test p =0.959). Conclusion: Measurement of the single-beat estimate of ventricular elastance (Ees(sb)) is possible in patients with severe aortic stenosis. Kelly's method (Ees(sb) = 0.9 × SBP/ESV) had the best agreement with the invasive measurement of left ventricular elastance (Ees). Systolic blood pressure, as measured by the brachial blood pressure cuff, has the best agreement with end-systolic pressure in severe aortic stenosis.

Stress echocardiography is widely used to detect coronary artery disease, but little evidence on downstream hospital costs in real-world practice is available. We examined how stress echocardiography accuracy and downstream hospital costs vary across NHS hospitals and identified key factors that affect costs to help inform future clinical planning and guidelines. Data on 7636 patients recruited from 31 NHS hospitals within the UK between 2014 and 2020 as part of EVAREST/BSE-NSTEP clinical study, were used. Data included all diagnostic tests, procedures, and hospital admissions for 12 months after a stress echocardiogram and were costed using the NHS national unit costs. A decision tree was built to illustrate the clinical pathway and estimate average downstream hospital costs. Multi-level regression analysis was performed to identify variation in accuracy and costs at both patient, procedural, and hospital level. Linear regression and extrapolation were used to estimate annual hospital cost-savings associated with increasing predictive accuracy at hospital and national level. Stress echocardiography accuracy varied with patient, hospital and operator characteristics. Hypertension, presence of wall motion abnormalities and higher number of hospital cardiology outpatient attendances annually reduced accuracy, adjusted odds ratio of 0.78 (95

AIMS Aortic valve area (AVA) used for echocardiographic assessment of aortic stenosis (AS) has been traditionally interpreted independently of sex, age and race. As differences in normal values might impact clinical decision-making, we aimed to establish sex-, age- and race-specific normative values for AVA and Doppler parameters using data from the World Alliance Societies of Echocardiography (WASE) Study. METHODS AND RESULTS Two-dimensional transthoracic echocardiographic studies were obtained from 1903 healthy adult subjects (48% women). Measurements of the left ventricular outflow tract (LVOT) diameter and Doppler parameters, including AV and LVOT velocity time integrals (VTIs), AV mean pressure gradient, peak velocity, were obtained according to ASE/EACVI guidelines. AVA was calculated using the continuity equation. Compared with men, women had smaller LVOT diameters and AVA values, and higher AV peak velocities and mean gradients (all P < 0.05). LVOT and AV VTI were significantly higher in women (P < 0.05), and both parameters increased with age in both sexes. AVA differences persisted after indexing to body surface area. According to the current diagnostic criteria, 13.5% of women would have been considered to have mild AS and 1.4% moderate AS. LVOT diameter and AVA were lower in older subjects, both men and women, and were lower in Asians, compared with whites and blacks. CONCLUSION WASE data provide clinically relevant information about significant differences in normal AVA and Doppler parameters according to sex, age, and race. The implementation of this information into clinical practice should involve development of specific normative values for each ethnic group using standardized methodology.

BACKGROUND:Left ventricular (LV) circumferential strain has received less attention than longitudinal deformation, which has recently become part of routine clinical practice. Among other reasons, this is because of the lack of established normal values. Accordingly, the aim of this study was to establish normative values for LV circumferential strain and determine sex-, age-, and race-related differences in a large cohort of healthy adults. METHODS:Complete two-dimensional transthoracic echocardiograms were obtained in 1,572 healthy subjects (51% men), enrolled in the World Alliance Societies of Echocardiography Normal Values Study. Subjects were divided into three age groups (<35, 35-55, and >55 years) and stratified by sex and by race. Vendor-independent semiautomated speckle-tracking software was used to determine LV regional circumferential strain and global circumferential strain (GCS) values. Limits of normal for each measurement were defined as 95% of the corresponding sex and age group falling between the 2.5th and 97.5th percentiles. Intergroup differences were analyzed using unpaired t tests. RESULTS:Circumferential strain showed a gradient, with lower magnitude at the mitral valve level, increasing progressively toward the apex. Compared with men, women had statistically higher magnitudes of regional and global strain. Older age was associated with a stepwise increase in GCS despite an unaffected ejection fraction, a decrease in LV volume, and relatively stable global longitudinal strain in men, with a small gradual decrease in women. Asian subjects demonstrated significantly higher GCS magnitudes than whites of both sexes and blacks among women only. In contrast, no significant differences in GCS were found between white and black subjects of either sex. Importantly, despite statistical significance of these differences across sex, age, and race, circumferential strain values were similar in all groups, with variations of the order of magnitude of 1% to 2%. Notably, no differences in GCS were found among brands of imaging equipment. CONCLUSION:This study established normal values of LV regional circumferential strain and GCS and identified sex-, age-, and race-related differences when present.

Mitral interventions remain technically challenging owing to the anatomical complexity and heterogeneity of mitral pathologies. As such, multi-disciplinary pre-procedural planning assisted by advanced cardiac imaging is pivotal to successful outcomes. Modern imaging techniques offer accurate 3D renderings of cardiac anatomy; however, users are required to derive a spatial understanding of complex mitral pathologies from a 2D projection thus generating an ‘imaging gap’ which limits procedural planning. Physical mitral modelling using 3D printing has the potential to bridge this gap and is increasingly being employed in conjunction with other transformative technologies to assess feasibility of intervention, direct prosthesis choice and avoid complications. Such platforms have also shown value in training and patient education. Despite important limitations, the pace of innovation and synergistic integration with other technologies is likely to ensure that 3D printing assumes a central role in the journey towards delivering personalised care for patients undergoing mitral valve interventions.

IntroductionScreening echocardiography, guided by the current World Heart Federation (WHF) criteria, has important limitations that impede the establishment of large-scale rheumatic heart disease (RHD) control programmes in endemic regions. The criteria misclassify a significant number of normal cases as borderline RHD. Prior attempts to simplify them are limited by incorporation bias due to the lack of an externally validated, accurate diagnostic test for RHD. We set out to assess novel screening criteria designed to avoid incorporation bias and to compare this against the performance of the current WHF criteria. MethodsThe performance of the WHF and the morpho-mechanistic (MM) RHD screening criteria (a novel set of screening criteria that evaluate leaflet morphology, motion and mechanism of regurgitation) as well as a simplified RHD MM 'rule-out' test (based on identifying a predefined sign of anterior mitral valve leaflet restriction for the mitral valve and any aortic regurgitation for the aortic valve) were assessed in two contrasting cohorts: first, a low-risk RHD cohort consisting of children with a very low-risk RHD profile. and second, a composite reference standard (CRS) RHD-positive cohort that was created using a composite of two criteria to ensure a cohort with the highest possible likelihood of RHD. Subjects included in this group required (1) proven, prior acute rheumatic fever and (2) current evidence of predefined valvular regurgitation on echocardiography. ResultsIn the low-risk RHD cohort (n=364), the screening specificities for detecting RHD of the MM and WHF criteria were 99.7% and 95.9%, respectively (p=0.0002). The MM rule-out test excluded 359/364 cases (98.6%). In the CRS RHD-positive cohort (n=65), the screening sensitivities for the detection of definite RHD by MM and WHF criteria were 92.4% and 89.2%, respectively (p=0.2231). The MM RHD rule-out test did not exclude any cases from the CRS RHD-positive cohort. ConclusionOur proposed MM approach showed an equal sensitivity to the WHF criteria but with significantly improved specificity. The MM RHD rule-out test excluded RHD-negative cases while identifying all cases within the CRS RHD-positive cohort. This holds promise for the development of a two-step RHD screening algorithm to enable task shifting in RHD endemic regions.

Transcatheter therapies for the treatment of structural heart diseases (SHD) have expanded dramatically over the last years, thanks to the developments and improvements of devices and imaging techniques, along with the increasing expertise of operators. Imaging, in particular echocardiography, is pivotal during patient selection, procedural monitoring, and follow-up. The imaging assessment of patients undergoing transcatheter interventions places demands on imagers that differ from those of the routine evaluation of patients with SHD, and there is a need for specific expertise for those working in the cath lab. In the context of the current rapid developments and growing use of SHD therapies, this document intends to update the previous consensus document and address new advancements in interventional imaging for access routes and treatment of patients with aortic stenosis and regurgitation, and mitral stenosis and regurgitation.

Background: Although increased left ventricular (LV) mass is associated with adverse outcomes, measured values vary widely depending on the specific technique used. Moreover, the impact of sex, age, and race on LV mass remains controversial, further limiting the clinical use of this parameter. Accordingly, the authors studied LV mass using a variety of two-dimensional and three-dimensional echocardiographic techniques in a large population of normal subjects encompassing a wide range of ages.Methods: Transthoracic echocardiograms obtained from 1,854 healthy adult subjects (52% men) enrolled in the World Alliance Societies of Echocardiography (WASE) Normal Values Study, were divided into three age groups (young, 18-35 years; middle aged, 36-55 years; and old, >55 years). LV mass was obtained using five conventional techniques, including linear and two-dimensional methods, as well as direct three-dimensional measurement. All LV mass values were indexed to body surface area, and differences according to sex, age, and race were analyzed for each technique. Results: LV mass values differed significantly among the five techniques. Three-dimensional measurements were considerably smaller than those obtained using the other techniques and were closer to magnetic reso-nance imaging normal values reported in the literature. For all techniques, LV mass in men was significantly larger than in women, with and without body surface area indexing. These technique-and sex-related differ-ences were larger than measurement variability. In women, age differences in LV mass were more pronounced and depicted significantly larger values in older age groups for all techniques, except three-dimensional echo-cardiography, which showed essentially no differences. LV mass was overall larger in black subjects than in white or Asian subjects.Conclusions: Significant differences in LV mass values exist across echocardiographic techniques, which are therefore not interchangeable. Sex-, race-, and age-related differences underscore the need for separate population specific normal values. (J Am Soc Echocardiogr 2023;36:533-42.)

Introduction: In mitral valve replacement (MVR), sudden increase in afterload and disruption of the annular-chordal-papillary-left-ventricular wall causes LV dysfunction in the early postoperative period. Preservation of the posterior mitral leaflet apparatus (MVR-P) has a favourable outcome on LV function. However, there is paucity of data on the impact of complete preservation of the sub-valvular apparatus (MVR-C). Objective: We investigated the impact of MVR-P and MVR-C on baseline and 3-months postoperative LV ejection fraction (EF) and global longitudinal strain (GLS). Methods: We retrospectively analysed a cohort of 29 MVR-P and 19 MVR-C patients with complete echo data at our unit, who were operated between 2012-2017. Between-group changes in LVEF and GLS were compared using independent sample T-test. Results: Median age was 59 years (IQR 50-69 years). Baseline LVEF was 58% (51 - 60%). Baseline GLS was -18.4 (-21.2 - -15.5). There were no significant differences between all baseline demographics including age (p=0.45), underlying MV pathology (p=0.1), baseline LVEF (p=0.48) and GLS (p=0.15). There was significantly less worsening of GLS in MVR-C group as compared to the MVR-P group (p=0.023), indicating better preservation of LV function. There was also a lower decrease in LVEF in the MVR-C as compared to the MVR-P group, although the difference was not statistically significant (p=0.23). Conclusion: MVR with complete preservation of the sub-valvular apparatus shows a favourable impact on the longitudinal function of the heart at 3 months. Further studies with larger patient numbers are indicated to investigate the long-term results of this surgical approach.

Background: Myocardial scar correlates with clinical outcomes. Traditionally, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is used to detect and quantify scar. In this prospective study using LGE CMR as reference, the authors hypothesized that nonlinear ultrasound imaging, namely, power modulation, can detect and quantify myocardial scar in selected patients with previous myocardial infarction. In addition, given the different histopathology between ischemic and nonischemic scar, a further aim was to test the diagnostic performance of this echocardiographic technique in unselected consecutive individuals with ischemic and nonischemic LGE or no LGE on CMR. Methods: Seventy-one patients with previous myocardial infarction underwent power modulation echocardiography following CMR imaging (group A). Subsequently, 101 consecutive patients with or without LGE on CMR, including individuals with nonischemic LGE, were scanned using power modulation echocardiography (group B). Results: In group A, echocardiography detected myocardial scar in all 71 patients, with good scar volume agreement with CMR (bias = -1.9 cm(3); limits of agreement [LOA], -8.0 to 4.2 cm(3)). On a per-segment basis, sensitivity was 82%, specificity 97%, and accuracy 92%. Sensitivity was higher in the inferior and posterior segments and lower in the anterior and lateral walls. In group B, on a per-subject basis, the sensitivity of echocardiography was 62% (91 % for ischemic and 30% for nonischemic LGE), with specificity and accuracy of 89% and 72%, respectively. The bias for scar volume between modalities was 5.9 cm(3), with LOA of 34.6 to 22.9 cm(3) (bias = -1.9 cm(3) [LOA, -11.4 to 7.6 cm(3)] for ischemic LGE, and bias = 18.9 cm(3) [LOA, -67.4 to 29.7.6 cm(3)] for nonischemic LGE). Conclusions: Power modulation echocardiography can detect myocardial scar in both selected and unselected individuals with previous myocardial infarction and has good agreement for scar volume quantification with CMR. In an unselected cohort with nonischemic LGE, sensitivity is low.

Importance Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration isrctn.com Identifier: ISRCTN57819173.

Background: Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear. Methods: Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples. Results: We included 430 patients (25% female) aged 64 +/- 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73-294) versus 87 (44-192) ng/L and 10 (6-13) versus 7 (4-11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%-73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (<= 5 ng/L cTnT and <= 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%. Conclusion: cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.

Background Acute kidney injury (AKI) is a frequent complication of transcatheter aortic valve implantation (TAVI) and has been linked to preexisting comorbidities, peri-procedural hypotension, and systemic inflammation. The extent of systemic inflammation after TAVI is not fully understood. Our aim was to characterize the inflammatory response after TAVI and evaluate its contribution to the mechanism of post-procedural AKI. Methods One hundred and five consecutive patients undergoing TAVI at our institution were included. We analyzed the peri-procedural inflammatory and oxidative stress responses by measuring a range of biomarkers (including C-reactive protein [hsCRP], cytokine levels, and myeloperoxidase [MPO]), before TAVI and 6, 24, and 48 hours post-procedure. We correlated this with changes in renal function and patient and procedural characteristics. Results We observed a significant increase in plasma levels of pro-inflammatory cytokines (hsCRP, interleukin 6, tumor necrosis factor alpha receptors) and markers of oxidative stress (MPO) after TAVI. The inflammatory response was significantly greater after transapical (TA) TAVI compared to transfemoral (TF). This was associated with a higher incidence of AKI in the TA cohort compared to TF (44% vs. 8%, respectively, p < 0.0001). The incidence of AKI was significantly lower when N-acetylcysteine (NAC) was given peri-procedurally (12% vs. 38%, p < 0.005). In multivariate analysis, only the TA approach and no use of NAC before the procedure were independent predictors of AKI. Conclusions TAVI creates a significant post-procedural inflammatory response, more so with the TA approach. Mechanisms of AKI after TAVI are complex. Inflammatory response, hypoperfusion, and oxidative stress may all play a part and are potential therapeutic targets to reduce/prevent AKI.

BACKGROUND:Although the assessment of right ventricular (RV) diastolic function is feasible, it has garnered far less momentum for use compared with its left ventricular counterpart. The scarcity of data defining normative RV diastolic function and the fact that implications of RV diastolic dysfunction in different disease states on outcomes are less well known both hinder integration into routine clinical assessment. The aim of this study was to establish normal values of RV diastolic parameters stratified by sex, age, and race using data from the World Alliance Societies of Echocardiography study. METHODS:A subset of 888 normal subjects from the World Alliance Societies of Echocardiography database were analyzed, including measurements of tricuspid valve (TV) inflow E- and A-wave velocities, E-wave deceleration time, and TV annular tissue Doppler e' and a' velocities. Additionally, right atrial (RA) maximal volume and RA peak reservoir strain were measured. Patients were grouped by age (<40, 41-65, and >65 years) and stratified by sex and race. Differences were analyzed using unpaired t tests. RESULTS:Compared with men, women had significantly higher TV e' and E-wave and A-wave velocities, though differences were modest. Increasing age was associated with stepwise lower TV E wave, e' velocity, and TV E/A ratio and higher a' velocity and E/e' ratio. RA peak reservoir strain was also lower, and RA end-systolic volume trended toward being smaller for older age groups. Asian subjects demonstrated significantly higher a' velocities, lower E wave, the smallest RA end-systolic volumes, and the lowest RA peak strain values compared with white subjects of both sexes. CONCLUSIONS:This study provides normal values for parameters used in the assessment of RV diastolic function stratified by race, sex, and age. The results demonstrate significant differences in RV diastolic parameters between age groups, which manifest in both individual parameters and composite ratios of TV inflow and annular velocities. Although limited sex- and race-related differences were also noted, age appears to have the most significant impact on RV diastolic parameters. These findings may aid in refining current normative values.

Echocardiography is less than 70 years old, and many major advances have occurred within living memory, but already some pioneering contributions may be overlooked. In order to consider what circumstances have been common to the most successful innovations, we have studied and here provide a timeline and summary of the most important developments in transthoracic and transoesophageal ultrasound imaging and Doppler techniques, as well as in intravascular ultrasound and imaging in paediatric cardiology. The entries are linked to a comprehensive list of first publications and to a collection of first-hand historical accounts published by early investigators. Review of the original manuscripts highlights that it is difficult to establish unequivocal precedence for many new imaging methods, since engineers were often working independently but simultaneously on similar problems. Many individuals who are prominently linked with particular developments were not the first in their field. Developments in echocardiography have been highly dependent on technological advances, and most likely to be successful when engineers and clinicians were able to collaborate with open exchange between centres and disciplines. As with many other new medical technologies, initial responses were sceptical and introduction into clinical practice required persistence and substantial energy from the first adopters. Current developments involve advances in software as much as in equipment, and progress will depend on continuing collaborations between engineers and clinical scientists, for example to identify unmet needs and to investigate the clinical impact of particular imaging approaches.

Background: Recent advances in mitral valve (MV) percutaneous interventions have escalated the need for a more quantitative and comprehensive assessment of the MV, which can be best achieved using three-dimensional echocardiography. Understanding normal valve size, structure, and function is essential for differentiation of healthy from disease states. The aims of this study were to establish normative values for MV apparatus size and morphology and to determine how they vary across age, sex, and race groups using data from the World Alliance Societies of Echocardiography Normal Values Study. Methods: Three-dimensional volumetric data sets obtained on transthoracic echocardiography in 748 normal subjects (51% men) were analyzed using commercial MV analysis software (TomTec Imaging Systems) to determine annular and leaflet dimensions and areas. The subjects were divided into groups by sex (378 men and 370 women) and age (18 to 40 years [n = 266], 41 to 65 years [n = 249], and >65 years [n = 233]) to identify sex- and age-related differences. In addition, differences among black, white, and Asian populations were studied. Inter- and intraobserver variability was assessed in a subset of 30 subjects and expressed as mean absolute difference between pairs of repeated measurements. Results: Compared with women, men had larger annular size measurements, larger tenting size parameters, and larger leaflet length and area. Compared with the black and white populations, the Asian population showed significantly smaller mitral annular size. Although many of the age, sex, and race differences in MV parameters were statistically significant, they were comparable with or smaller than the corresponding measurement variability. Indexing to body surface area and height did not eliminate these differences consistently, suggesting that parameters may need to be indexed according to their dimensionality. Conclusions: This analysis of the World Alliance Societies of Echocardiography data provides normative values of mitral apparatus size and morphology. Although sex- and age-related differences were noted, they need to be interpreted with caution in view of the associated measurement variability. (J Am Soc Echocardiogr 2022;35:738-51.)

Focus Echocardiography has routinely been used to offer quick diagnosis in critical care environments, predominantly by clinicians with limited training. During the COVID-19 pandemic, international guidance recommended all echocardiography scans were performed as focus studies to limit operator viral exposure in both inpatient and outpatient settings. The aim of this study was to assess the effectiveness of eFoCUS, a focus scan performed by fully trained echocardiographers following a minimum dataset plus full interrogation of any pathology found.All diagnostic echocardiograms, performed by fully trained echocardiographers during an 8-week period during the first UK COVID-19 wave, were included. The number of images acquired was compared in the following categories: admission status, COVID status, image quality, indication, invasive ventilation, pathology found, echocardiographer experience, and whether eFoCUS was deemed adequate to answer the clinical question.In 87.4% of the 698 scans included, the operator considered that the eFOCUS echo protocol, with additional images when needed, was sufficient to answer the clinical question on the request. Echocardiographer experience did not affect the number of images acquired. Less images were acquired in COVID-19 positive patients compared to negative/asymptomatic (38 ± 12 vs. 42 ± 12, p = .001), and more images were required when a valve pathology was identified.eFoCUS echocardiography is an effective protocol for use during the COVID-19 pandemic. It provides sufficient diagnostic information to answer the clinical question but differs from standard focus/limited protocols by enabling the identification and interrogation of significant pathology and incidental findings, preventing unnecessary repeat scans and viral exposure of operators.

BACKGROUND:Transthoracic echocardiography is the leading cardiac imaging modality for patients admitted with COVID-19, a condition of high short-term mortality. The aim of this study was to test the hypothesis that artificial intelligence (AI)-based analysis of echocardiographic images could predict mortality more accurately than conventional analysis by a human expert. METHODS:Patients admitted to 13 hospitals for acute COVID-19 who underwent transthoracic echocardiography were included. Left ventricular ejection fraction (LVEF) and left ventricular longitudinal strain (LVLS) were obtained manually by multiple expert readers and by automated AI software. The ability of the manual and AI analyses to predict all-cause mortality was compared. RESULTS:In total, 870 patients were enrolled. The mortality rate was 27.4% after a mean follow-up period of 230 ± 115 days. AI analysis had lower variability than manual analysis for both LVEF (P = .003) and LVLS (P = .005). AI-derived LVEF and LVLS were predictors of mortality in univariable and multivariable regression analysis (odds ratio, 0.974 [95% CI, 0.956-0.991; P = .003] for LVEF; odds ratio, 1.060 [95% CI, 1.019-1.105; P = .004] for LVLS), but LVEF and LVLS obtained by manual analysis were not. Direct comparison of the predictive value of AI versus manual measurements of LVEF and LVLS showed that AI was significantly better (P = .005 and P = .003, respectively). In addition, AI-derived LVEF and LVLS had more significant and stronger correlations to other objective biomarkers of acute disease than manual reads. CONCLUSIONS:AI-based analysis of LVEF and LVLS had similar feasibility as manual analysis, minimized variability, and consequently increased the statistical power to predict mortality. AI-based, but not manual, analyses were a significant predictor of in-hospital and follow-up mortality.