How to prevent rubella epidemics and congenital rubella syndrome: lessons from 42 years of longitudinal epidemiology in Osaka Prefecture, Japan (1982-2023).

BACKGROUND: Despite the introduction of rubella-containing vaccine into routine immunization in 1977, rubella has not been eliminated in Japan. This study aimed to validate the immunization strategy and to highlight the crucial elements of elimination program. METHODS: We scrutinized cases of rubella and congenital rubella syndrome (CRS). Additionally, we analyzed the national vaccination coverage, seroprevalence, and number of maternal rubella-related spontaneous or artificial fetal deaths. RESULTS: The shift from selective to universal immunization significantly reduced rubella cases coupled with increased seroprevalence in children. However, rubella resurged in 2012-2013 and 2018-2019, which was virologically and serologically confirmed to be associated with imported rubella virus (RuV) and susceptible males. Although the disease burden of CRS may have been suppressed in the past by the large number of spontaneous or artificial fetal deaths, the incidence rate of CRS was comparable to that of the 1960s to 1980s. Cases of breakthrough infection and CRS were identified in females who were considered to have a history of single-dose vaccination. CONCLUSIONS: Even with universal immunization, future epidemics and severe outcomes cannot be prevented unless immunization gaps are closed. Furthermore, CRS and breakthrough infection are not completely prevented by single-dose vaccination, indicating the need for second-dose vaccination.

Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses.

Virus-like particles (VLPs) provide a well-established vaccine platform; however, the immunogenic properties acquired by VLP structure remain poorly understood. In this study, we showed that systemic vaccination with norovirus VLP recalls human IgA responses at higher magnitudes than IgG responses under a humanized mouse model that was established by introducing human PBMCs in severely immunodeficient mice. The recall responses elicited by VLP vaccines depended on VLP structure and the disruption of VLP attenuated recall responses, with a more profound reduction being observed in IgA responses. The IgA-focusing property was also conserved in a murine norovirus-primed model under which murine IgA responses were recalled in a manner dependent on VLP structure. Importantly, the VLP-driven IgA response preferentially targeted virus-neutralizing epitopes located in the receptor-binding domain. Consequently, VLP-driven IgA responses were qualitatively superior to IgG responses in terms of the virus-neutralizing activity in vitro. Furthermore, the IgA in mucosa obtained remarkable protective function toward orally administrated virus in vivo. Thus, our results indicate the immune-focusing properties of the VLP vaccine that improve the quality/quantity of mucosal IgA responses, a finding with important implications for developing mucosal vaccines.

A Heterodimeric Antibody Fragment for Passive Immunotherapy Against Norovirus Infection.

Human noroviruses cause an estimated 685 million infections and 200 000 deaths annually worldwide. Although vaccines against GII.4 and GI.1 genotypes are under development, no information is available regarding vaccines or monoclonal antibodies to other noroviral genotypes. Here, we developed 2 variable-domain llama heavy-chain antibody fragment (VHHs) clones, 7C6 and 1E4, against GII.4 and GII.17 human noroviruses, respectively. Although 7C6 cross-reacted with virus-like particles (VLPs) of GII.17, GII.6, GII.3, and GII.4, it neutralized only GII.4 norovirus. In contrast, 1E4 reacted with and neutralized only GII.17 VLPs. Both VHHs blocked VLP binding to human induced pluripotent stem cell-derived intestinal epithelial cells and carbohydrate attachment factors. Using these 2 VHHs, we produced a heterodimeric VHH fragment that neutralized both GII.4 and GII.17 noroviruses. Because VHH fragments are heat- and acid-stable recombinant monoclonal antibodies, the heterodimer likely will be useful for oral immunotherapy and prophylaxis against GII.4 and GII.17 noroviruses in young, elderly, or immunocompromised persons.

Clinical and Prognostic Values of ALBI Score in Patients With Acute Heart Failure.

BACKGROUND: Although liver dysfunction is one of the common complications in patients with acute heart failure (AHF), no integrated marker has been defined. The albumin-bilirubin (ALBI) score has recently been proposed as a novel, clinically-applicable scoring system for liver dysfunction. We investigated the utility of the ALBI score in patients with AHF compared to that for a preexisting liver dysfunction score, the Model of End-Stage Liver Disease Excluding prothrombin time (MELD XI) score. METHODS: We evaluated ALBI and MELD XI scores in 1,190 AHF patients enrolled in the prospective, multicentre Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure study. The associations between the two scores and the clinical profile and prognostic predictive ability for 1-year mortality were evaluated. RESULTS: The mean MELD XI and ALBI scores were 13.4±4.8 and -2.25±0.48, respectively. A higher ALBI score, but not higher MELD XI score, was associated with findings of fluid overload. After adjusting for pre-existing prognostic factors, the ALBI score (HR 2.11, 95% CI: 1.60-2.79, p<0.001), but not the MELD XI score (HR 1.02, 95% CI: 0.99-1.06, p=0.242), was associated with 1-year mortality. Likewise, area under the receiver-operator-characteristic curves for 1-year mortality significantly increased when the ALBI score (0.71 vs. 0.74, p=0.020), but not the MELD XI score (0.71 vs. 0.72, p=0.448), was added to the pre-existing risk factors. CONCLUSIONS: The ALBI score is potentially a suitable liver dysfunction marker that incorporates information on fluid overload and prognosis in patients with AHF. These results provide new insights into heart-liver interactions in AHF patients.

Clinical value of enzyme immunoassay that detects rubella-specific immunoglobulin M immediately after disease onset.

A total of 300 patients with nucleic acid test-confirmed rubella, mostly adults, were investigated to determine the clinical value of a rubella-specific IgM test using an EIA kit. IgM titers increased after rash onset, the median IgM titer being significantly higher 3 days post-onset than on previous days (P < 0.0001). Similarly, the IgM-positive rate at 3 days post-onset (61.5%) was significantly higher than on previous days (P < 0.0001). This IgM test against rubella at 3 days or more post-disease onset provides the clinically relevant information.

Specialty-Related Differences in the Acute-Phase Treatment and Prognosis in Patients With Acute Heart Failure　- Insights From REALITY-AHF.

BACKGROUND: The aim of this study was to assess specialty-related differences in the treatment for patients with acute heart failure (AHF) in the acute phase and subsequent prognostic differences. Methods and Results: We analyzed hospitalizations for AHF in REALITY-AHF, a multicenter prospective registry focused on very early presentation and treatment in patients with AHF. All patients were classified according to the medical specialty of the physicians responsible for contributed most to decisions regarding the initial diagnosis and treatment after the emergency department (ED) arrival. Patients initially managed by emergency physicians (n=614) or cardiologists (n=911) were analyzed. After propensity-score matching, vasodilators were used less often by emergency physicians than by cardiologists at 90 min after ED arrival (29.8% vs. 46.1%, P<0.001); this difference was also observed at 6, 24, and 48 h. Cardiologists administered furosemide earlier than emergency physicians (67 vs. 102 min, P<0.001). However, the use of inotropes, noninvasive ventilation, and endotracheal intubation were similar between groups. In-hospital mortality did not differ between patients managed by emergency physicians and those managed by cardiologists (4.1% vs. 3.8%, odds ratio 1.12; 95% confidence interval 0.58-2.14). CONCLUSIONS: Despite differences in initial management, no prognostic difference was observed between emergency physicians and cardiologists who performed the initial management of patients with AHF.

FGFR1 Analyses in Four Patients with Hypogonadotropic Hypogonadism with Split-Hand/Foot Malformation: Implications for the Promoter Region.

Heterozygous loss-of-function mutations of FGFR1 (fibroblast growth factor receptor 1) cause various disorders including hypogonadotropic hypogonadism with split-hand/foot malformation (HH-SHFM). We examined FGFR1 in four Japanese patients with HH-SHFM (cases 1-4) and the mother of case 4 with HH only. Cases 1 and 2 had heterozygous loss-of-function mutations with no dominant negative effect (c.289G>A, p.[G97S]; and c.2231G>C, p.[R744T]), and case 3 had a splice donor site mutation (c.1663+1G>T). Notably, case 4 had a maternally inherited 8,312 bp microdeletion that involved noncoding exon 1U and impaired FGFR1 expression. Furthermore, consistent with the presence of transcription-related histone marks (e.g., H3K4Me3, H3K4Me1, and H3K27Ac) and multiple transcription factor-binding sites around exon 1U, functional studies demonstrated a marked transactivation function of a 414-bp segment harboring the transcription start site. These results support the relevance of FGFR1 mutations to HH-SHFM, and argue for the presence of the FGFR1 core-promoter elements around exon 1U.

Association of Apical Longitudinal Rotation with Right Ventricular Performance in Patients with Pulmonary Hypertension: Insights into Overestimation of Tricuspid Annular Plane Systolic Excursion.

BACKGROUND: Current guidelines recommend the routine use of tricuspid annular plane systolic excursion (TAPSE) as a simple method for estimating right ventricular (RV) function. However, when ventricular apical longitudinal rotation (apical-LR) occurs in pulmonary hypertension (PH) patients, it may result in overestimated TAPSE. METHODS: We studied 105 patients with PH defined as mean pulmonary artery pressure >25 mmHg at rest measured by right heart cardiac catheterization. TAPSE was defined as the maximum displacement during systole in the RV-focused apical four-chamber view. RV free-wall longitudinal speckle tracking strain (RV-free) was calculated by averaging 3 regional peak systolic strains. The apical-LR was measured at the peak rotation in the apical region including both left and right ventricle. The eccentricity index (EI) was defined as the ratio of the length of 2 perpendicular minor-axis diameters, one of which bisected and was perpendicular to the interventricular septum, and was obtained at end-systole (EI-sys) and end-diastole (EI-dia). Twenty age-, gender-, and left ventricular ejection fraction-matched normal controls were studied for comparison. RESULTS: The apical-LR in PH patients was significantly lower than that in normal controls (-3.4 ± 2.7° vs. -1.3 ± 1.9°, P = 0.001). Simple linear regression analysis showed that gender, TAPSE, EI-sys, and EI-dia/EI-sys were associated with apical-LR, but RV-free was not. Multiple regression analysis demonstrated that gender, EI-dia/EI-sys, and TAPSE were independent determinants of apical-LR. CONCLUSIONS: TAPSE may be overestimated in PH patients with clockwise rotation resulting from left ventricular compression. TAPSE should thus be evaluated carefully in PH patients with marked apical rotation.

Long-term viral shedding and viral genome mutation in norovirus infection.

The duration of viral shedding in the patients from two outbreaks and four sporadic cases of norovirus (NoV) infections was investigated. The longest period of viral shedding into feces was for 173 days in an inpatient from one case of outbreak. The VP1 sequence from two long-term viral shedding cases in the outbreak revealed four synonymous and one non-synonymous mutations in one inpatient at 26 days from the onset of illness, and nine synonymous and two non-synonymous mutations and a deletion, 10 synonymous mutations and a deletion in other inpatient at 29 days and 54 days from the onset of illness, respectively. Ten of the 11 amino acid positions detected in these two inpatients were in the outermost P2 domain of the viral capsid protein, and mutations at positions 295, 297, and 394 were shared in the inpatients. Mutations in the P2 domain were in epitopes A and D or near epitopes A, C, and E, suggesting that the long-term carrier state of norovirus infection contributes to the generation of escape mutants by host immunoselection.

Association of left atrial booster-pump function with heart failure symptoms in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

BACKGROUND: Identification of heart failure (HF) symptoms in patients with severe aortic stenosis (AS) and preserved left ventricular (LV) ejection fraction (EF) is clinically important, but assessment of HF symptoms is challenging. It was recently reported that resting left atrium (LA) functions are related to exercise performance and are also important prognostic markers for patients with HF. The aim of this study was to assess the association of the HF symptoms with LA function in patients with severe AS and preserved LVEF. METHODS: We retrospectively studied 40 patients with severe AS and preserved LVEF (all ≥50%) who were referred for aortic valve replacement (AVR). LA reservoir (SR-LAs), conduit (SR-LAe), and booster-pump (SR-LAa) functions were determined as the averaged global LA speckle tracking longitudinal strain rate from apical four- and two-chamber views. Twenty patients were symptomatic and 20 asymptomatic. RESULTS: Aortic stenosis severity was similar for the 2 groups. Symptomatic status was associated with age, LV mass index, hemoglobin, B-type natriuretic peptide, LV end-systolic volume index, LVEF, LA volume index, SR-LAs, SR-LAe, and SR-LAa. Importantly, multivariate logistic regression analysis revealed that SR-LAa was the only independent determinant of symptomatic status (OR = 0.242, P = 0.002). Furthermore, significant improvement of SR-LAa was observed along with the reduction in LA volume index and LV mass index after AVR. CONCLUSIONS: SR-LAa was found to be associated with the HF symptoms. Characterization of LA booster-pump function may be useful for the assessment of the symptomatic status in patients with severe AS patients and limited physical activity.

Impact of Right Ventricular Geometry on Mitral Regurgitation After Transcatheter Closure of Atrial Septal Defect.

Worsening of mitral regurgitation (MR) is sometimes observed after closure of an atrial septal defect (ASD). However, since the mechanism of this deterioration remains unclear, the aim of our study was to investigate the effect of left (LV) and right ventricular (RV) geometry on MR after transcatheter closure of ASD.We studied 27 patients with ASD who underwent transcatheter closure. Echocardiography was performed before and 6 ± 2 months after the procedure. In addition to conventional echocardiographic parameters, full volume data of the whole LV and RV heart was obtained with 3-dimensional echocardiography. MR was quantified by measuring the width of the vena contracta, and was graded as mild (< 3.0 mm), moderate (3.0 to 6.9 mm), or severe (≥ 7.0 mm).Ten patients (37%) were classified as having worsening MR and the remaining 17 (63%) as not having worsening MR. The two groups showed similar baseline characteristics, except for patients with worsening MR being more likely to be older (P = 0.009) and having a larger left-to-right shunt of pulmonary and systemic blood flow ratio (P = 0.02). It is noteworthy that the horizontal-to-vertical ratio of basal-RV at end-systole for patients with worsening MR was significantly smaller than that for patients without worsening MR (1.0 ± 0.2 versus 1.4 ± 0.2, P < 0.0001). Furthermore, multivariate analysis showed that the horizontal-to-vertical ratio of basal-RV at end-systole was the independent predictor of worsening MR during follow-up (P < 0.001).RV geometry may affect MR after closure of ASD. The pre-operative horizontal-to-vertical ratio of basal-RV is considered useful for predicting worsening of MR after closure of ASD.

Left ventricular endocardial dysfunction in patients with preserved ejection fraction after receiving anthracycline.

BACKGROUND: Anthracycline chemotherapy generates progressive dose-dependent left ventricular (LV) dysfunction associated with a poor prognosis. Early detection of minor LV myocardial dysfunction caused by the cardiotoxicity of anthracycline is thus important for predicting global LV dysfunction. METHODS: Fifty patients with preserved ejection fraction (all ≥55%) after receiving anthracycline chemotherapy were recruited for this study. Two-dimensional speckle tracking was used to assess global radial and circumferential strains from mid-LV short-axis views and global longitudinal strain from the apical four- and two-chamber view as peak global strain curves. Three-dimensional (3D) radial, circumferential, and longitudinal myocardial function was quantified as a peak global strain curve using 3D speckle tracking from all 16 LV segments. 3D speckle tracking imaging was used to evaluate LV endocardial area change ratio (area strain) quantified as peak global area strain curve (3D-GAS) to determine LV endocardial function. Twenty age-, gender-, and EF-matched normal volunteers were studied for comparisons. RESULTS: Only 3D-GAS and peak 3D global circumferential strains of the anthracycline group were significantly worse than those of the control group (-43.3 ± 3.1 vs. -45.8 ± 4.3% and -31.6 ± 3.5% vs. -34.4 ± 4.2%, respectively; P = 0.008, P = 0.004) even though global LV systolic and diastolic functions were similar. 3D-GAS correlated significantly with the cumulative doxorubicin dose (r = 0.316, P = 0.026). It was noteworthy that multivariate analysis showed only 3D-GAS (ß = 0.323, P = 0.025) was independently associated with cumulative doxorubicin dose. CONCLUSIONS: Three-dimensional speckle tracking area strain was found useful for early detection of minor LV endocardial dysfunction associated with the use of anthracycline, and may thus prove to be clinically useful for predicting global LV dysfunction.

Combined baseline strain dyssynchrony index and its acute reduction predicts mid-term left ventricular reverse remodeling and long-term outcome after cardiac resynchronization therapy.

The objective of this study was to test the hypothesis that combining assessment of baseline radial strain dyssynchrony index (SDI), that expressed both left ventricular (LV) dyssynchrony and residual myocardial contractility, and of acute changes in this index can yield more accurate prediction of mid-term responders and long-term outcome after cardiac resynchronization therapy (CRT). Radial SDI for 75 CRT patients was calculated as the average difference between peak and end-systolic speckle tracking strain from 6 segments of the mid-LV short-axis view before and 8 ± 2 days after CRT. Mid-term responder was defined as ≥ 15% decrease in LV end-systolic volume 6 ± 2 months after CRT. Long-term outcome was tracked over 5 years. Baseline radial SDI ≥ 6.5% is considered predictive of responder and favorable outcome, as previously reported. Acute reduction in radial SDI ≥ 1.5% was found to be the best predictor of mid-term responders with CRT. Furthermore, patients with acute reductions in radial SDI ≥1.5% were associated with a significantly more favorable long-term outcome after CRT than those with radial SDI <1.5% (log rank P < 0.001). An important findings were that baseline radial SDI ≥6.5% and acute reductions in radial SDI ≥ 1.5% in 42 patients were associated with the highest event-free survival rate of 92%, whereas, 21 patients corresponding values of <6.5% and <1.5% were associated with low event-free survival rate of 46% (log rank P < 0.001). Combined assessment of baseline radial SDI and its acute reduction after CRT may have clinical implications for predicting responders and thus patients' care.

Prognostic impact of early aortic volume changes at hospital discharge in patients with acute type B aortic dissection.

BACKGROUND: Early prediction of aorta-related events is important for determining subsequent treatment strategies in patients with acute aortic dissection. However, most studies evaluated long-term aortic growth rates by annual assessment. The purpose of our study was to determine whether the in-hospital growth rate of aortic volume was associated with aorta-related events. METHODS: We studied 116 patients with uncomplicated type B acute aortic dissection. We analyzed whether changes in aortic volume were associated with aorta-related events during a 5-year follow-up. According to the growth rate from admission to discharge, patients were divided into two groups: Increase >0 (aortic volume: n = 59, aortic diameter: n = 43) and Reduction ≤0 (aortic volume: n = 57, aortic diameter: n = 73) in maximum aortic diameter or aortic volume. The primary endpoint was the discriminative ability of the growth rate of aortic volume for aorta-related events. RESULTS: According to the evaluation of aortic volume changes, the Increase group had significantly higher aorta-related event rates than those in the Reduction group (49.2 % vs. 3.5 %, respectively; p < 0.001). Receiver operating characteristics analysis showed that the growth rate of aortic volume had a clearly useful discrimination, with an area under the curve of 0.84, whereas the discriminative ability of the growth rate of maximum aortic diameter was poor (area under the curve: 0.53). Multivariate analysis showed that the growth rate of aortic volume from admission to discharge was an independent predictor of aorta-related events (hazard ratio, 26.3; 95 % confidence interval, 2.04-286.49; p = 0.001). CONCLUSIONS: In-hospital evaluation of aortic volume was helpful to predict long-term aorta-related events in patients with uncomplicated type B acute aortic dissection.

Dynamic left ventricular dyssynchrony assessed on 3-dimensional speckle-tracking area strain during dobutamine stress has a negative impact on cardiovascular events in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Left ventricular (LV) dyssynchrony is not a stable phenomenon, but rather, changes dynamically. Given that the prognostic impact of dynamic dyssynchrony has not yet been elucidated, the objective was to investigate the clinical impact of dynamic dyssynchrony on patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: Seventy DCM patients with ejection fraction 32±9% were retrospectively recruited, and 3-dimensional speckle-tracking area strain was used to measure both contractile reserve and changes in dyssynchrony during dobutamine stress. The standard deviation of time-to-peak area strain was adopted as the systolic dyssynchrony index. Event-free survival was then tracked over a 13-month period. A ≥7.55% increase in systolic dyssynchrony index during dobutamine stress (Δsystolic dyssynchrony index) was the best predictor of cardiovascular events with 77% sensitivity and 88% specificity. Multivariate Cox analysis indicated that not only the absence of contractile reserve (Δglobal area strain ≤21.1%: hazard ratio [HR], 15.29; P=0.01), but the presence of dynamic dyssynchrony (ΔLV dyssynchrony ≥7.55%: HR: 7.591; P=0.003) was an independent predictor of cardiovascular events. Importantly, absence of dynamic dyssynchrony and presence of contractile reserve were associated with the most favorable outcome (98%), whereas the reverse condition was associated with the worst outcome (20%, P<0.001). CONCLUSIONS: Dynamic dyssynchrony is a potential predictor of cardiovascular events in patients with DCM, while assessment of dynamic dyssynchrony in combination with contractile reserve may further improve prognostic risk stratification.

Haemodynamic effects of inhaled nitric oxide in acute myocardial infarction complicated by right heart failure under ECPELLA support: case report.

Background: Recently, mechanical support obtained with the combination of venoarterial extracorporeal membrane oxygenation (VA-ECMO) and an Impella device, together referred to as ECPELLA, has been shown to be effective for acute myocardial infarction with cardiogenic shock. However, methods for withdrawing VA-ECMO in acute myocardial infarction cases complicated by right ventricular dysfunction are yet to be established. Here, we report the effective use of inhaled nitric oxide during the weaning of VA-ECMO from the ECPELLA management of a patient with acute myocardial infarction with cardiogenic shock. Case summary: An 81-year-old man with an acute extensive anterior wall myocardial infarction with cardiogenic shock was supported with ECPELLA to improve his haemodynamics. During ECPELLA, the Impella device could not maintain sufficient flow. Echocardiography revealed a small left ventricle and an enlarged right ventricle, indicating acute right heart failure. Inhaled nitric oxide was initiated to reduce right ventricle afterload, which decreased pulmonary artery pressure from 34/20 to 27/13 mmHg, improved right and left ventricle sizes, and stabilized the Impella support. Afterward, VA-ECMO could be withdrawn because the Impella alone was sufficient for haemodynamic support. Discussion: Inhaled nitric oxide improved right ventricle performance in a patient with severe myocardial infarction with right heart failure supported by ECPELLA. Thus, we suggest that inhaled nitric oxide facilitates the weaning of VA-ECMO from patients with refractory right ventricular dysfunction who are supported by ECPELLA.

Risk factors related to psychological distress among elderly patients with cardiovascular disease.

AIMS: Psychological distress is associated with poor prognosis in patients with cardiovascular disease (CVD). However, factors related to psychological distress in elderly patients with CVD are less understood. We aim to investigate the rate of psychological distress in elderly patients with CVD in comparison with that of patients without CVD and to examine the clinical, socio-economic, and lifestyle factors associated with this condition. METHODS AND RESULTS: Data from a nationwide population-based study in Japan of patients aged ≥60 years were extracted, and 1:1 propensity score matching was conducted of patients with and without CVD. Psychological distress was assessed using the K6 scale, on which a score ≥6 was defined as psychological distress. Of the 24 388 matched patients, the rate of psychological distress was significantly higher among patients with CVD compared with those without CVD (29.8 vs. 20.5%, P < 0.0001). The multivariate analysis revealed that female sex, comorbidities, except for hypertension, current smoking status, daily sleep duration of <6 vs. ≥8 h, home renter vs. owner, retired status, having a walking disability, and lower monthly household expenditure were independently associated with psychological distress. Walking disability was observed to be in greatest association with psychological distress (odds ratio 2.69, 95% confidence interval 2.46-2.93). CONCLUSION: Elderly patients with CVD were more likely to have psychological distress compared with those without CVD. Multiple factors, including clinical, socio-economic, and lifestyle variables, were associated with psychological distress. These analyses may help healthcare providers to identify high-risk patients with psychological distress in a population of older adults with CVD.

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.

Variations in indexation of left atrial volume across different races.

Background: Left atrial volume (LAV) has prognostic value. Guidelines propose indexation to body surface area (BSA), however studies demonstrate this can overcorrect for body size. Limited studies investigate indexation across different ethnicities. We sought to evaluate the effect of ethnicity on indexation. Methods: Using data from the World Alliance of Societies of Echocardiography (WASE) cohort, healthy subjects were classified by race as White, Black, Asian, or Other. Biplane LAV was indexed to traditional isometric measurements (BSA, height, weight, ideal body weight (IBW) and IBW derived BSA (IBSA)), as well as previously-derived allometric height exponents (2.7 and 1.72). Additionally, an allometric height exponent for our cohort was derived (linear regression of the logarithmic transformation of LAV = a(height)b) as 1.87. All indices were then assessed using Spearman correlation, with a good index retaining correlation of LAV/index to raw LAV (r∼1), while avoiding overcorrection by the index (r∼0). Results: There were 1366 subjects (White: 524, Black: 149, Asian: 523, Other: 170; median age 44 years, 653 females (47.8%)). In the entire group, BSA, IBSA, height1.87 and height1.72 performed well with retaining correlation to raw LAV (r > 0.9 for all), and minimising overcorrection to body size (r < 0.1 for all). On race-specific analysis, BSA overcorrected for body size in the White population (r = 0.128). Height1.72 minimised overcorrection for body size in all populations (r ≤ 0.1 for all races). Conclusion: Despite a cohort with normal BMI, there was still disparity in LAV indexation with BSA across races. Allometric height indexation, particularly using height1.72, is a possible solution, although further validation studies in BMI extremes are required.

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.