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).

Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation.

BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.

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.

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.

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.

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.

Brain natriuretic peptide measurements using standard biochemical equipment: Comparisons with conventional immunoassays.

BACKGROUND: Brain natriuretic peptide (BNP) is an essential cardiac biomarker for diagnosing heart failure and for prognoses in patients with various cardiac diseases. However, measurement requires immunological assays that are not available in every hospital. Recently, a novel BNP kit (Nanopia BNP-A, Sekisui Inc.; BNPn) that uses general-purpose, automated, biochemical analyzers has become commercially available. We assessed how its accuracy and utility compare with those of conventional immunological tests. METHODS AND RESULTS: We retrospectively collected 1491 conventional BNP measurements (BNPc), which had been clinically indicated for BNP testing and for which residual samples were still stored in the laboratory. We measured BNP using the novel kit and determined the correlation of BNP levels between the two methods. We also assessed the predictive value of both BNP measurements for major cardiac events (MACEs). The analytical performance of both measuring methods was similar. Log-transformed BNP measured by both methods showed strong correlation (r = 0.92); however, log-transformed BNPn was significantly higher than log-transformed BNPc (p<0.001). BNPc of 200 ng/L was used to stratify patients into two groups. According to the regression formula between the two methods, we determined a cut-off value of BNPn as 250 ng/L. During a median of 15 months of follow-up, 43 MACEs developed. Both BNPc and BNPn were associated with MACEs. Kaplan-Meier survival analysis indicated that both BNPc and BNPn cut-off values stratified the high-risk group for prognostication. The diagnostic and prognostic utilities were proven even if the lower cut-off values (BNPc = 100 ng/L, BNPn = 130 ng/L) were employed. CONCLUSIONS: A new BNP measurement using biochemical equipment provides prognostic value similar to that of conventional BNP analysis; thus, it should prove useful in hospitals in which conventional immunological examinations are not available.

Prognostic Value of Right Ventricular Strains Using Novel Three-Dimensional Analytical Software in Patients With Cardiac Disease.

Background: Right ventricular (RV) three-dimensional (3D) strains can be measured using novel 3D RV analytical software (ReVISION). Our objective was to investigate the prognostic value of RV 3D strains. Methods: We retrospectively selected patients who underwent both 3D echocardiography (3DE) and cardiac magnetic resonance from January 2014 to October 2020. 3DE datasets were analyzed with 3D speckle tracking software and the ReVISION software. The primary end point was a composite of cardiac events, including cardiac death, heart failure hospitalization, or ventricular tachyarrhythmia. Results: 341 patients were included in this analysis. During a median of 20 months of follow-up, 49 patients reached a composite of cardiac events. In univariate analysis, 3D RV ejection fraction (RVEF) and three 3D strain values [RV global circumferential strain (3D RVGCS), RV global longitudinal strain (3D RVGLS), and RV global area strain (3D RVGAS)] were significantly associated with cardiac death, ventricular tachyarrhythmia, or heart failure hospitalization (Hazard ratio: 0.88 to 0.93, p < 0.05). Multivariate analysis revealed that 3D RVEF, three 3D strain values were significantly associated with cardiac events after adjusting for age, chronic kidney disease, and left ventricular systolic/diastolic parameters. Kaplan-Meier survival curves showed that 3D RVEF of 45% and median values of 3D RVGCS, 3D RVGLS, and 3D RVGAS stratified a higher risk for survival rates. Classification and regression tree analysis, including 22 clinical and echocardiographic parameters, selected 3D RVEF (cut-off value: 34.5%) first, followed by diastolic blood pressure (cut-off value: 53 mmHg) and 3D RVGAS (cut-off value: 32.4%) for stratifying two high-risk group, one intermediate-risk group, and one low-risk group. Conclusions: RV 3D strain had an equivalent prognostic value compared with 3D RVEF. Combining these parameters with 3D RVEF may allow more detailed stratification of patient's prognosis in a wide array of cardiac diseases.

Prognostic Value of the Three-Dimensional Right Ventricular Ejection Fraction in Patients With Asymptomatic Aortic Stenosis.

Background: The right ventricular (RV) function is an important prognostic marker of asymptomatic aortic stenosis (AS). However, previous publications have not addressed the additive value of conventional RV parameters over left heart parameters. Whether three-dimensional echocardiography (3DE)-derived RV ejection fraction (RVEF) has prognostic utility independent of 3DE derived left heart parameters is also unknown. We investigated the prognostic utility of 3DE RVEF in patients with asymptomatic AS. Methods: We retrospectively selected 392 asymptomatic AS patients. RVEF, left ventricular ejection fraction (LVEF) and left atrial volumes (LAVs) were measured using 3DE datasets. We determined the association of those parameters, as well as of aortic valve replacement (AVR), and Charlson's comorbidity index with cardiac events. We also analyzed whether RVEF has incremental value over two-dimensional echocardiography (2DE) RV parameters. Results: During a median follow-up of 27 months, 57 patients developed cardiac events, and 68 patients received AVR. Univariate Cox proportional hazard analysis revealed that RVEF was associated with cardiac events (p < 0.001). Multivariate analysis revealed that RVEF was significantly associated with cardiac events (p < 0.001) even after adjusting for AVR, Charlson's comorbidity index, LVEF, LAV, E/e', and indexed aortic valve area (iAVA). An incremental value of RVEF over left heart parameters was also demonstrated using a nested regression model. Classification and regression-tree analysis selected RVEF first with a cut-off value of 41%. RVEF had incremental value over iAVA, LVEF, and 2DE conventional RV parameters for its association with future outcomes. Conclusions: 3DE RVEF had significant prognostic value even after adjusting for comorbidities, left heart parameters, and conventional 2DE RV parameters in asymptomatic aortic stenosis.

Does reactogenicity after a second injection of the BNT162b2 vaccine predict spike IgG antibody levels in healthy Japanese subjects?

BACKGROUND: Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech's BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). METHODS AND RESULTS: Blood samples were obtained from 67 Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0-11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% confidence interval (95% CI): 855-1282 AU/mL) after the first injection to 17,378 AU/mL (95% CI: 14,622-20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, AE score after the first injection, and log-transformed spike IgG after the first injection. CONCLUSIONS: Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.

Therapeutic efficacy of direct oral anticoagulants and vitamin K antagonists for left ventricular thrombus: Systematic review and meta-analysis.

BACKGROUND: Although several meta-analyses have compared efficacies of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for treatment of left ventricular thrombus (LVT), those meta-analyses included no single-arm studies. METHODS AND RESULTS: PubMed, Scopus, and the Cochrane Library databases were searched for articles investigating thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, or all-cause death in LVT treated with VKAs or DOACs, and single-class meta-analyses were also included (PROSPERO database, CRD42021230849). Event rates were pooled using a random effects model. Meta-regression analysis was performed to explore factors that may influence outcomes. 2,612 patients from 23 articles were included (VKAs: 2,004, DOACs: 608). There were no significant differences between VKAs and DOACs in the frequency of thrombus resolution (VKAs: 0.75 [95% confidence interval; 0.67 to 0.81], DOACs: 0.75 [0.67 to 0.82]), stroke (VKAs: 0.06 [0.04 to 0.10], DOACs: 0.02 [0.01 to 0.01]), any thromboembolism (VKAs: 0.08 [0.05 to 0.13], DOACs: 0.03 [0.01 to 0.10]), major bleeding (VKAs: 0.06 [0.04 to 0.09], DOACs: 0.03 [0.01 to 0.06]), any bleeding (VKAs: 0.08 [0.05 to 0.12], DOACs: 0.08 [0.06 to 0.10]), and all-cause death (VKAs: 0.07 [0.04 to 0.13], DOACs: 0.09 [0.05 to 0.16]). Meta-regression analysis revealed that increased duration of follow-up was associated with lower-rates of stroke (estimate: -0.040, p = 0.0495) with VKAs, but not with DOACs. There was significant publication bias for thrombus resolution, stroke, any thromboembolism, any bleeding, and all-cause death. CONCLUSIONS: Efficacy and adverse outcomes of therapy with DOACs and VKAs do not differ. Randomized controlled trials are needed to determine the optimal anticoagulant strategy.

Prognostic value of the left ventricular - left atrial volume ratio assessed using three-dimensional echocardiography with fully automated analytical software.

BACKGROUND: we investigated the prognostic value of a new 3D echocardiography (3DE) parameter, the left ventricular-left atrial volume ratio (LVLAVR) in a diverse group of subjects. METHODS: 3DE full-volume datasets were analyzed in 307 patients using fully automated LV and LA quantification software (Dynamic Heart Model, Philips Medical Systems, Andover, MA, USA), which generated LV and LA volume curves using artificial intelligence and 3D speckle tracking technology. We measured LVLAVR at LV end-diastole (edLVLAVR; LV end-diastolic volume / LA minimal volume), LVLAVR at LV end-systole (esLVLAVR: LV end-systolic volume / LA maximal volume), and their differences (ΔLVLAVR: edLVLAVR - esLVLAVR). No manual editing was performed on data of any patient. The primary endpoint was a major adverse cardiac event (MACE), including cardiac death, heart failure resulting in hospitalization, myocardial infarction, or ventricular tachyarrhythmia. RESULTS: feasibility of LVLAVR measurements was 90%. During a median follow-up of 21 months, 43 patients developed a primary endpoint. Univariate Cox proportional hazard analysis revealed that edLVLAVR [hazard ratio (HR): 0.72, p < 0.01] and ΔLVLAVR (HR: 0.62, p < 0.01) were significantly associated with MACE. Median values of both edLVLAVR (4.59) and ΔLVLAVR (2.90) successfully stratified patients into high- and low-risk populations for future MACEs. ΔLVLAVR was still significantly associated with MACEs after adjusting for age, chronic kidney disease (CKD) and LV ejection fraction or after adjusting for age, CKD, and E/ε'. CONCLUSIONS: LVLAVR provided incremental value over traditional LV systolic and diastolic function parameters to predict future adverse outcomes. The analysis was fully automated, thereby eliminating measurement variability.

Reliability of left atrial strain reference values: A 3D echocardiographic study.

BACKGROUND: Standard apical four-chamber and two-chamber views often maximize the long-axis of the left ventricle, resulting in artifactitious foreshortening of the left atrium (LA), which may overestimate LA longitudinal reservoir strain (LALS). We compared LALS values between 2D echocardiography (2DE) and 3D echocardiography (3DE) in healthy subjects to determine whether 2DE speckle tracking analysis overestimates the reference value of LALS. METHODS AND RESULTS: In this study, 4 types of cohorts were included: 1. 105 normal subjects (retrospectively), 2. 53 patients with cardiovascular diseases (retrospectively), 3. 15 patients who received cardiac magnetic resonance (prospectively), and 4. 20 normal subjects (prospectively). LALS and LA length were measured using both 2DE and 3DE in 105 healthy subjects (median age: 42 years). Biplane LALS was measured in apical four- and two-chamber views using 2DE speckle tracking software, and 3DE LALS was measured using new 3DE LA strain software. To determine sensitivity, we also performed the same analysis in 53 patients with cardiovascular disease. The mean value of biplane LALS was 39.6%. LA length at both end-diastole (r = -0.43) and end-systole (r = -0.54) was negatively correlated with biplane LALS. Multivariate regression analysis revealed that both end-diastolic and end-systolic LA length had significant negative relationships with biplane LALS after adjusting for anthropometric and echocardiographic image quality parameters. 3DE LALS (23.7±7.6%) gave significantly lower values than 2DE LALS (39.5±12.0%, p<0.001) with a weak correlation (r = 0.33). LA length measured by 2DE was significantly shorter than that measured by 3DE. The same trend was observed in diseased patients. CONCLUSIONS: Our results revealed that in 2DE, the LA cavity consistently appears longitudinally foreshortened in apical views, potentially overestimating LALS. 3DE may overcome this limitation.

Prognostic Value of the Right Ventricular Ejection Fraction, Assessed by Fully Automated Three-Dimensional Echocardiography: A Direct Comparison of Analyses Using Right Ventricular-Focused Views versus Apical Four-Chamber Views.

BACKGROUND: Right ventricular (RV) three-dimensional echocardiographic (3DE) data sets are acquired from either the RV-focused view (RVFV) or the apical four-chamber view (4CV). The prognostic value of 3DE RV ejection fraction (RVEF) was investigated using fully automated RV quantification software, and how measurement values with 3DE data sets from the RVFV compare with those from the 4CV was determined. METHODS: One hundred seventy-four patients who had undergone both cardiac magnetic resonance (CMR) and 3DE imaging were retrospectively selected. RV 3DE data sets were acquired from both the RVFV and the 4CV and were analyzed separately using fully automated RV quantification software. Primary end points were cardiac events, including cardiac death, heart failure requiring hospitalization, nonfatal myocardial infarction, and ventricular tachyarrhythmia. RESULTS: The feasibility of RVEF measurements on 3DE imaging from the RVFV and 4CV was 92% and 92%, respectively. There was good correlation (r = 0.83) and small bias (0.3%) between RVEF from the RVFV and that from the 4CV. Similar results were obtained when only data from patients whose echocardiograms had poor image quality in one or both views were analyzed (r = 0.83, bias = 1.7%, n = 78). Although fully automated analysis in both the RVFV and 4CV significantly underestimated RV volumes compared with CMR, neither measurement differed significantly for RVEF compared with CMR. During a median follow-up period of 12.5 months, 21 patients experienced primary end points. RVEF assessed by CMR and 3DE imaging was significantly associated with cardiac events. RVEF using fully automated analysis had a significant association with cardiac events, even in patients with poor image quality (RVFV: hazard ratio, 0.90 [P = .009, n = 44]; 4CV: hazard ratio, 0.90 [P = .009, n = 68]). CONCLUSIONS: RV 3DE data sets from the RVFV and 4CV yielded similar RVEF values using fully automated software. RVEFs from both approaches had significant association with outcomes. Thus, both provide accurate information regarding RV function and risk for adverse outcomes.

Prognostic value of automated longitudinal strain measurements in asymptomatic aortic stenosis.

OBJECTIVE: Two-dimensional (2D) longitudinal strain (LS) predicts cardiac events in aortic stenosis (AS). However, it requires manual editing, which affects its accuracy and reliability. We investigated whether left ventricular (LV), left atrial (LA) and right ventricular (RV) LSs using fully automated 2D strain software provide useful prognostic information in asymptomatic AS. METHODS: We performed LS analyses in 340 asymptomatic patients with AS using novel, fully automated 2D strain analytical software (AutoStrain, Philips) to obtain LV global LS (LVGLS), LALS, RV free wall LS and RVLS. The primary end point was a composite of cardiac events, including cardiac death, heart failure hospitalisation, myocardial infarction or ventricular tachyarrhythmia. RESULTS: During a median of 24 months follow-up, 46 patients reached a primary end point. 62 patients had aortic valve surgery. All four LSs were significantly associated with the primary end point using univariate analysis (HR 0.821 to 0.951, p<0.05). Multivariate analysis revealed that LVGLS (HR 0.873 to 0.888, p<0.05) remained significantly associated with cardiac events, even after adjusting haemodynamic measures of AS severity and LV ejection fraction. Kaplan-Meier survival curve showed median values of both LVGLS (cut-off: 15.1%) and LALS (cut-off: 22.3%) provide a significant difference in cardiac event rate (3-year event-free rate; LVGLS: 89% vs 76%, p=0.002; LALS: 89% vs 76%, p=0.001). Classification and regression-tree analysis, including four LSs, clinical characteristics and traditional echocardiographic parameters, selected LVGLS and E/ε' for stratifying a high-risk group of patients with cardiac events. CONCLUSIONS: Fully automated 2D LS analysis, especially LVGLS provides useful prognostic information in asymptomatic AS.