Prognostic value of right ventricular free-wall longitudinal strain in patients with pulmonary hypertension: systematic review and meta-analyses.

BACKGROUND: Right ventricular (RV) dysfunction is associated with adverse outcomes in patients with pulmonary hypertension (PH). This systematic review and meta-analysis evaluated the prognostic value of RV free-wall longitudinal strain (RVfwLS), compared with other RV parameters in PH. METHODS: We searched for articles presenting the HR of two-dimensional RVfwLS in PH. HRs were standardised using the within-study SD. The ratio of HRs of a 1 SD change in RVfwLS versus systolic pulmonary arterial pressure (SPAP), systolic tricuspid annular velocities (s'-TV), RV fractional area change (FAC) or tricuspid annular plane systolic excursion (TAPSE) was calculated for each study, after which we conducted a random model meta-analysis. Subgroup analysis regarding the type of outcome, aetiology of PH and software vendor was also performed. RESULTS: Twenty articles totalling 2790 subjects were included. The pooled HR of a 1 SD decrease of RVfwLS was 1.80 (95% CI: 1.62 to 2.00, p<0.001), and there was a significant association with all-cause death (ACD) and composite endpoints (CEs). The ratio of HR analysis revealed that RVfwLS has a significant, strong association with ACD and CE per 1 SD change, compared with corresponding values of SPAP, s'-TV, RVFAC or TAPSE. RVfwLS was a significant prognostic factor regardless of the aetiology of PH. However, significant superiority of RVfwLS versus other parameters was not observed in group 1 PH. CONCLUSIONS: The prognostic value of RVfwLS in patients with PH was confirmed, and RVfwLS is better than other RV parameters and SPAP. Further accumulation of evidence is needed to perform a detailed subgroup analysis for each type of PH. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000052679).

Limitations of Apical Sparing Pattern in Cardiac Amyloidosis: A Multicenter Echocardiographic Study.

BACKGROUND: Although impaired left ventricular (LV) global longitudinal strain (GLS) with apical sparing is a feature of cardiac amyloidosis (CA), its diagnostic accuracy has varied across studies. We aimed to determine the ability of apical sparing ratio (ASR) and most common echocardiographic parameters to differentiate patients with confirmed CA from those with clinical and/or echocardiographic suspicion of CA, but with this diagnosis ruled out. METHODS: We identified 544 patients with confirmed CA and 200 controls as defined above (CTRL Patients). Measurements from transthoracic echocardiograms (TTE) were performed using artificial intelligence software (Us2.AI, Singapore) and audited by an experienced echocardiographer. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic performance and optimal cutoffs for the differentiation of CA patients from CTRL Patients. Additionally, a group of 174 healthy subjects (Healthy CTRL) was included to provide insight on how Patients and Healthy controls differed echocardiographically. RESULTS: LV GLS was more impaired (-13.9 ± 4.6% vs -15.9 ± 2.7%, p < 0.0005) and ASR was higher (2.4 ± 1.2 vs 1.7 ± 0.9, p < 0.0005) in the CA group vs. CTRL Patients. Relative wall thickness and ASR were the most accurate parameters for differentiating CA from CTRL Patients (AUC: 0.77 and 0.74, respectively). However, even with the optimal cutoff of 1.67, ASR was only 72% sensitive and 66% specific for CA, indicating presence of apical sparing in 32% of CTRL Patients and even in 6% Healthy CTRLs. CONCLUSIONS: Apical sparing did not prove to be a CA-specific biomarker for accurate identification of CA, when compared to clinically similar controls with no CA.

Prognostic value of right ventricular free-wall longitudinal strain in aortic stenosis: A systematic review and meta-analysis.

BACKGROUND: Assessment of right ventricular (RV) function in aortic stenosis (AS) may improve risk stratification. However, whether the prognostic value of RV free-wall longitudinal strain (RVfwLS) is better than that of other right heart or pulmonary circulation parameters remains uncertain. This study assessed and compared the prognostic value of RVfwLS with traditional parameters in the AS population using a systematic review and meta-analysis. METHODS: We selected studies reporting the hazard ratio (HR) of RVfwLS in patients with AS. We also collected data regarding the HR of systolic pulmonary arterial pressure (SPAP), fractional area change (FAC), and tricuspid annulus plane systolic excursion (TAPSE). To ensure comparability, we standardized the HR using within-study standard deviations. The comparison between the prognostic value of RVfwLS and other parameters was conducted as a ratio of HR. RESULTS: This meta-analysis included 9 studies comprising a total of 2547 patients, with 679 events. The pooled HR of RVfwLS was 1.56 (95 % CI: 1.39-1.75, p < 0.001). When examining the ratio of HR between RVfwLS and conventional parameters, all comparisons were statistically non-significant [RVfwLS/SPAP: 1.28 (95 % CI: 0.99-1.65, p = 0.06); RVfwLS/FAC: 1.24 (95 % CI: 0.90-1.72, p = 0.14); and RVfwLS/TAPSE:1.07 (95 % CI: 0.75-1.52, p = 0.60)]. CONCLUSIONS: This meta-analysis establishes a substantial association between RVfwLS and adverse outcomes in the AS population. However, comparative analysis between RVfwLS and SPAP, FAC, or TAPSE did not support the prognostic superiority of RVfwLS.

Normal Values of Echocardiographic Right Ventricular Size and Systolic Function Measurements in a Healthy Japanese Population　- Subanalysis of the WASE Study.

Background: Although accurate assessment of right ventricular (RV) morphology and function is clinically important, data regarding reference values for echocardiographic measurements of the right ventricle in the Japanese population are limited. Methods and Results: The World Alliance Society of Echocardiography (WASE) Normal Values Study was conducted to examine normal echocardiographic values in 15 countries. Using the WASE study database, we analyzed 2-dimensional echocardiographic parameters of RV size and systolic function in 192 healthy Japanese individuals and compared them with those obtained from 153 healthy American individuals. In the Japanese population, the absolute values of RV dimensions were smaller for women than men, although the difference disappeared after the data were adjusted for body surface area. RV dimensions, RV length and RV area were smaller in the elderly, but age did not affect RV systolic function. The absolute value, but not the adjusted value, of RV size tended to be smaller in Japanese than American individuals for both sexes. For men, RV systolic function parameters were lower in the Japanese population. This trend was not seen in women. Conclusions: The present study identified normal reference values for RV size and systolic function in a healthy Japanese population. Sex, age, and race had a significant impact on RV size; however, this trend was weak for RV systolic function.

Trial sequential analysis of efficacy and safety of direct oral anticoagulants and vitamin K antagonists against left ventricular thrombus.

Meta-analysis may increase the risk of random errors. Trial sequential analysis (TSA) has been developed to adjust for these random errors. We conducted TSA on the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in left ventricular thrombus (LVT) patients in order to estimate how many additional patients should be required to draw definite conclusions. PubMed, Scopus, and Cochrane Library databases were searched for articles directly comparing DOACs and VKAs for LVT in LV thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, and all-cause death. TSA was conducted with a cumulative Z-curve, monitoring boundaries, and required sample size. A simulated trial was run and TSA estimated the sample sizes of trials needed to draw definite conclusions. Of 4749 articles, 25 studies were used for the analysis. TSA revealed the current sample size already demonstrated superiority of DOACs in LV thrombus resolution and stroke, and futility in any thromboembolism and all-cause death. Two other outcomes did not achieve the required sample size. The sample size of new trials needed to demonstrate the superiority of DOACs over VKAs was estimated 400 for any bleeding. Corresponding trials needed to demonstrate no significant differences could be estimated for major bleeding and any bleeding (n = 200 and n = 2000, respectively). Current results show that the sample size required to draw definite conclusions was not reached for two outcomes, and there was a risk of random error. Further randomized controlled trials with sample sizes estimated by TSA will work effectively to obtain valid conclusions.

Prognostic value of the right ventricular ejection fraction using three-dimensional echocardiography: Systematic review and meta-analysis.

AIMS: Three-dimensional echocardiography (3DE) is a robust method for measuring the right ventricular (RV) ejection fraction (EF), which is closely associated with outcomes. We performed a systematic review and meta-analysis (1) to examine the prognostic value of RVEF and (2) to compare its prognostic value with that of left ventricular (LV) EF and LV global longitudinal strain (GLS). We also performed individual patient data analysis to validate the results. METHODS AND RESULTS: We searched articles reporting the prognostic value of RVEF. Hazard ratios (HR) were re-scaled using the within-study standard deviation (SD). To compare predictive values of RVEF and LVEF or LVGLS, the ratio of HR related to a 1-SD reduction of RVEF versus LVEF or LVGLS was calculated. Pooled HR of RVEF and pooled ratio of HR were analyzed in a random-effects model. Fifteen articles with 3,228 subjects were included. Pooled HR of a 1-SD reduction of RVEF was 2.54 (95% confidence interval (CI): 2.15-3.00). In subgroup analysis, RVEF was significantly associated with outcome in pulmonary arterial hypertension (PAH) (HR: 2.79, 95% CI: 2.04-3.82) and cardiovascular (CV) diseases (HR: 2.23, 95%CI: 1.76-2.83). In studies reporting HRs for both RVEF and LVEF or RVEF and LVGLS in the same cohort, RVEF had 1.8-fold greater prognostic power per 1-SD reduction than LVEF (ratio of HR: 1.81, 95%CI: 1.20-2.71), but had predictive value similar to that of LVGLS (ratio of HR: 1.10, 95%CI: 0.91-1.31) and to LVEF in patients with reduced LVEF (ratio of HR: 1.34, 95%CI: 0.94-1.91). In individual patient data analysis (n = 1,142), RVEF < 45% was significantly associated with worse CV outcome (HR: 4.95, 95% CI: 3.66-6.70), even in patients with reduced or preserved LVEF. CONCLUSIONS: The findings of this meta-analysis highlight and support the use of RVEF assessed by 3DE to predict CV outcomes in routine clinical practice in patients with CV diseases and in those with PAH.

Deep Learning-Based Prediction of Right Ventricular Ejection Fraction Using 2D Echocardiograms.

BACKGROUND: Evidence has shown the independent prognostic value of right ventricular (RV) function, even in patients with left-sided heart disease. The most widely used imaging technique to measure RV function is echocardiography; however, conventional 2-dimensional (2D) echocardiographic assessment is unable to leverage the same clinical information that 3-dimensional (3D) echocardiography-derived right ventricular ejection fraction (RVEF) can provide. OBJECTIVES: The authors aimed to implement a deep learning (DL)-based tool to estimate RVEF from 2D echocardiographic videos. In addition, they benchmarked the tool's performance against human expert reading and evaluated the prognostic power of the predicted RVEF values. METHODS: The authors retrospectively identified 831 patients with RVEF measured by 3D echocardiography. All 2D apical 4-chamber view echocardiographic videos of these patients were retrieved (n = 3,583), and each subject was assigned to either the training or the internal validation set (80:20 ratio). Using the videos, several spatiotemporal convolutional neural networks were trained to predict RVEF. The 3 best-performing networks were combined into an ensemble model, which was further evaluated in an external data set containing 1,493 videos of 365 patients with a median follow-up time of 1.9 years. RESULTS: The ensemble model predicted RVEF with a mean absolute error of 4.57 percentage points in the internal and 5.54 percentage points in the external validation set. In the latter, the model identified RV dysfunction (defined as RVEF <45%) with an accuracy of 78.4%, which was comparable to an expert reader's visual assessment (77.0%; P = 0.678). The DL-predicted RVEF values were associated with major adverse cardiac events independent of age, sex, and left ventricular systolic function (HR: 0.924 [95% CI: 0.862-0.990]; P = 0.025). CONCLUSIONS: Using 2D echocardiographic videos alone, the proposed DL-based tool can accurately assess RV function, with similar diagnostic and prognostic power as 3D imaging.

Normal Values of Three-Dimensional Right Ventricular Size and Function Measurements: Results of the World Alliance Societies of Echocardiography Study.

BACKGROUND: Normal values for three-dimensional (3D) right ventricular (RV) size and function are not well established, as they originate from small studies that involved predominantly white North American and European populations, did not use RV-focused views, and relied on older 3D RV analysis software. The World Alliance Societies of Echocardiography study was designed to generate reference ranges for normal subjects around the world. The aim of this study was to assess the worldwide capability of 3D imaging of the right ventricle and report size and function measurements, including their dependency on age, sex, and ethnicity. METHODS: Healthy subjects free of cardiac, pulmonary, and renal disease were prospectively enrolled at 19 centers in 15 countries, representing six continents. Three-dimensional wide-angle RV data sets were obtained and analyzed using dedicated RV software (TomTec) to measure end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume, and ejection fraction (EF). Results were categorized by sex, age (18-40, 41-65, and >65 years) and ethnicity. RESULTS: Of the 2,007 subjects with attempted 3D RV acquisitions, 1,051 had adequate image quality for confident measurements. Upper and lower limits for body surface area-indexed EDV, ESV, and EF were 48 and 95 mL/m2, 19 and 43 mL/m2, and 44% and 58%, respectively, for men and 42 and 81 mL/m2, 16 and 36 mL/m2, and 46% and 61%, respectively, for women. Men had significantly larger EDVs, ESVs, and stroke volumes (even after body surface area indexing) and lower EFs than women (P < .05). EDV and ESV did not show any meaningful differences among age groups. Three-dimensional RV volumes were smallest in Asians. CONCLUSIONS: Reliability of 3D RV acquisition is low worldwide, underscoring the importance of future improvements in imaging techniques. Sex and race must be taken into consideration in the assessment of both RV volumes and EF.

Analysis of Left Ventricular Indexes and Mortality Among Asian Adults With Hemodynamically Significant Chronic Aortic Regurgitation.

Importance: Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown. Objective: To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021. Exposures: Aortic regurgitation severity, graded by a comprehensive integrated approach. Main Outcomes and Measures: The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF. Results: Of 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid-ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2). Conclusions and Relevance: This multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.

Application of Allometric Methods for Indexation of Left Ventricular End-Diastolic Volume to Normal Echocardiographic Data and Assessing Gender and Racial Differences.

BACKGROUND: Gender and racial differences in cardiac chamber size are vital to establish normal ranges of cardiac chamber size in healthy subjects. Many studies report either nonindexed raw measurements or measurements indexed to isometric body surface area (BSA) when establishing normal reference values. Other studies advocate allometric indexation for standardization of heart size. We compared several allometric methods on gender and racial differences in left ventricular end-diastolic volume (LVEDV) measured on three-dimensional echocardiography. METHODS: Three-dimensional echocardiographic LVEDV data from the World Alliance Societies of Echocardiography normal values study were indexed to isometric BSA, BSA1.5, BSA1.8, isometric height, height2.3, height2.9, and estimated lean body mass. Gender, racial, national, and regional differences in indexed and nonindexed LVEDV were assessed using Cohen's d statistic or Cohen's f statistic, according to the number of groups being compared. Cohen's d < 0.20 and Cohen's f < 0.10 were regarded as very small relative magnitudes of difference. RESULTS: Differences in LVEDV among White, Black, and Asian races were smallest when BSA1.5 or BSA1.8 was used for indexation, followed by estimated lean body mass. LVEDV/BSA1.5 was nearly identical for men and women (very small, d = 0.05). However, both LVEDV/BSA1.5 and LVEDV/BSA1.8 still provided moderate relative magnitudes of difference (f = 0.22-0.37) among geographic regions. Specifically, among Asians, Indians had the smallest LVEDV/BSA1.5 (1.8). Brazilians had the smallest LVEDV/BSA1.5 (1.8) among Whites. CONCLUSIONS: Gender and racial differences in LVEDV became smaller when LVEDV was indexed to BSA1.5 or BSA1.8. However, differences in LVEDV among nations remain even after applying allometric scaling. This finding suggests that differences in body composition and/or hemodynamics are potentially more important determinants of heart size than race or gender.

Age-, Sex-, and Race-Based Normal Values for Left Ventricular Circumferential Strain from the World Alliance Societies of Echocardiography Study.

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.

Left ventricular volume and ejection fraction measurements by fully automated 3D echocardiography left chamber quantification software versus CMR: A systematic review and meta-analysis.

BACKGROUND: Although transthoracic three-dimensional echocardiography (3DE) is now recommended by guidelines for left ventricular (LV) volumetric measurements, widespread implementation has been limited due to time constraints and required expertise. We hypothesized that fully automated 3DE left chamber quantification software might provide accurate measurements, and that its application could eliminate these obstacles. METHODS: To address this hypothesis, we conducted a systematic review and meta-analysis following a search for studies that compared LV volumes and ejection fraction (EF) using fully automated 3DE software (HeartModel or Dynamic HeartModel, Philips Healthcare, Andover, MA, USA) with cardiac magnetic resonance (CMR), from 2015 to 2021. A random effects model was used to determine biases, correlations, and 95 % confidence intervals (CI) of LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF. Subgroup and meta-regression analyses were performed to determine effects of moderators on the outcome. RESULTS: Of 12 studies (616 subjects), mean differences and 95 % CIs in EDV, ESV, and EF between fully automated 3DE software and CMR were -19.6 mL (95 % CI; -27.6 to -11.5 mL), -11.4 mL (-16.7 to -6.2 mL), and 0.4 % (-1.1 to 2.0 %), respectively. Corresponding correlation values between the two methods were 0.91 (0.86-0.94), 0.89 (0.82-0.93), and 0.85 (0.81-0.88), respectively. Meta-regression analysis revealed that there were no effects of either publication year, type of software, or type of analysis on the outcome of LV volumetric and functional parameters except for publication year on LVESV correlation values. CONCLUSIONS: Although 3DE still underestimates LV volumes, the observed differences were no >20 mL. EF showed similar values to CMR. Excellent correlations between the two techniques make fully automated 3DE left chamber quantification software useful for routine clinical practice in adult population.

Normal Values of Left Ventricular Mass by Two-Dimensional and Three-Dimensional Echocardiography: Results from the World Alliance Societies of Echocardiography Normal Values Study.

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 resonance 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 differences 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 echocardiography, 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.

Normative values of the aortic valve area and Doppler measurements using two-dimensional transthoracic echocardiography: results from the Multicentre World Alliance of Societies of Echocardiography Study.

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.

Comparison Between Bicuspid and Tricuspid Aortic Regurgitation: Presentation, Survival, and Aorta Complications.

Background: Although the Asian population is growing globally, data in Asian subjects regarding differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in aortic regurgitation (AR) remain unexplored. Objectives: The aim of this study was to examine differences between Asian BAV-AR and TAV-AR in significant AR, including aorta complications. Methods: The study included 711 consecutive patients with chronic moderate to severe and severe AR from 2008 to 2020. Outcomes included all-cause death, aortic valve surgery (AVS), and incidence of aortic dissection (AD). Results: There were 149 BAV-AR (mean age: 48 ± 16 years) and 562 TAV-AR (mean age: 68 ± 15 years; P < 0.0001) patients; baseline indexed left ventricle and indexed aorta size were larger in TAV-AR. Total follow-up was 4.8 years (IQR: 2.0-8.4 years), 252 underwent AVS, and 185 died during follow-up; 18 cases (only 1 BAV) of AD occurred, with a mean maximal aorta size of 60 ± 9 mm. The 10-year AVS incidence was higher in TAV-AR (51% ± 4%) vs BAV-AR (40% ± 5%) even after adjustment for covariates (P < 0.0001). The 10-year survival was higher in BAV-AR (86% ± 4%) vs TAV-AR (57% ± 3%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). Post-AVS 10-year survival was 93% ± 5% in BAV-AR and 78% ± 5% in TAV-AR, respectively (P = 0.08). The 10-year incidence of AD was higher in TAV-AR (4.8% ± 1.5%) than in BAV-AR (0.9% ± 0.9%) and was determined by aorta size ≥45 mm (P ≤ 0.015). Compared with an age- and sex-matched population in Taiwan, TAV-AR (HR: 3.1) had reduced survival (P < 0.0001). Conclusions: Our findings suggest that TAV-AR patients were at a later stage of AR course and had a high AD rate as opposed to BAV-AR patients in Taiwan, emphasizing the importance of early referral for timely management. Surgery on the aorta with a lower threshold in TAV-AR should be considered.

Prognostic Value of Apical Sparing of Longitudinal Strain in Patients with Symptomatic Aortic Stenosis.

Background: Older patients with aortic stenosis (AS) have a higher incidence of wild-type transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to determine whether apical sparing of longitudinal strain (LS) could help diagnose ATTR-CA and provide useful prognostic information in symptomatic AS. Methods: We performed vendor-independent two-dimensional speckle-tracking analysis of regional and global left ventricular LS in 16 patients with ATTR-CA and 31 patients with non-obstructive hypertrophic cardiomyopathy to determine the best cutoff value of the apical sparing ratio (APSR) for diagnosing ATTR-CA. We then determined the prevalence in patients who had an APSR higher than the best cutoff value and investigated its prognostic value in 230 patients with symptomatic AS. To determine the natural history of symptomatic AS, patients who had aortic valve replacement were censored at the time of surgery. Results: The best cutoff value of APSR was 0.76. APSR ≥ 0.76 was observed in 108 patients with symptomatic AS (48%). The prevalence was not different among the four AS subgroups. During a median follow-up period of 5.7 months, 47 patients had cardiac events. Cox proportional hazards analysis revealed that neither APSR nor APSR ≥ 0.76 was significantly associated with future cardiac events. Conclusions: Apical sparing was frequently observed in patients with symptomatic AS, and it was not a useful predictor of future adverse outcomes. Our results suggest that the underlying cause of apical sparing in AS may not be related to the presence of ATTR-CA.

Temporal changes in spike IgG levels after two doses of BNT162b2 vaccine in Japanese healthcare workers: Do spike IgG levels at 3 months predict levels 6 or 8 months after vaccination?

BACKGROUND: Accurate timing of BNT162b2 boosters to prevent breakthrough infections of coronavirus disease 2019 (COVID-19) requires reliable estimates of immune status. We hypothesized that spike IgG levels at 3 months after two doses of the BNT162b2 vaccine might predict subsequent spike IgG levels. METHODS AND RESULTS: Spike IgG levels were tested at 3, 6, and 8 months after the second dose of the BNT162b2 vaccine in 251 Japanese health care workers (median age: 39 years, female: 187). The median level of spike IgG was 2,882 AU/mL at 3 months. This decreased to 875 AU/mL at 6 months and 579 AU/mL at 8 months. There were good correlations of log-transformed spike IgG levels between 3 and 6 months (r = 0.86) and between 3 and 8 months (r = 0.82). The correlation further improved after excluding three subjects who had possible COVID-19 infections (r = 0.91, r = 0.86). Log-transformed spike IgG levels at 6 or 8 months yields the following equation: log spike IgG at 6 (8) months = 0.92 (0.86) X log spike IgG at 3 months- 0.23 (0.18). Predicted spike IgG at 6 months of ≥ 300 or < 300 AU/mL had 98% sensitivity, 47% specificity, and 94% accuracy for discriminating subjects whose actual spike IgG titers at 6 months were above or below 300 AU/mL. Corresponding values of predicted spike IgG at 8 months were 97%, 70%, and 93%, respectively. CONCLUSIONS: We conclude that predictive formulae using spike IgG levels at 3 months after two-dose vaccination with BNT162b2 reliably estimate subsequent spike IgG levels up to 8 months and provide useful information in terms of vaccination booster timing.