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.

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.

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.

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.

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.

Optimal timing of echocardiography for heart failure inpatients in Japanese institutions: OPTIMAL Study.

AIMS: Guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) provided by the European Society of Cardiology state that echocardiography is recommended for the assessment of the myocardial structure and function of subjects with suspected HF including HF with reduced (HFrEF), mid-range (HFmrEF), and preserved ejection fraction (HFpEF) as class I of recommendation and level C of evidence. However, the impact of timing of echocardiography on survival for hospitalized HF patients or the prevalence of echocardiography during their stay has not yet been fully investigated. Therefore, we designed and conducted a prospective multicentre study, Optimal Timing of Echocardiography for Heart Failure Inpatients in Japanese Institutions (OPTIMAL) study, to investigate and evaluate the prevalence of echocardiography during the in-hospital stay of HF patients, and the impact of timing of echocardiography on their survival. METHODS AND RESULTS: OPTIMAL was based on a nationwide, prospective, multicentre registry at 10 institutions in Japan endorsed by the Japanese Society of Echocardiography. A total of 601 patients hospitalized with HF were enrolled between August 2016 and July 2018 at the participating centres. Their mean age was 73.9 ± 13.0 years, left ventricular ejection fraction was 37.0% (26.0-50.0), and 256 patients (42.6%) were female. Admission echocardiography (admission echo) was categorized as either standard or point-of-care echocardiography performed within 3 days of admission, as was pre-discharge echocardiography (pre-discharge echo) within 3 days of discharge. The primary endpoint was defined as cardiovascular death over a median follow-up period of 18.9 months (9.3-26.5 months). Admission echo was performed for 476 patients (79.2%) and pre-discharge echo for 216 patients (35.9%). The primary endpoint of cardiovascular death occurred in 65 patients (10.8%). Kaplan-Meier curve findings indicated that survival of patients with pre-discharge echo was significantly better than that of patients without it (log-rank P < 0.001), and the same findings were obtained for patients with HFrEF, HFmrEF, and HFpEF. However, survival of patients with and without admission echo was similar (log-rank P = 0.33). CONCLUSIONS: This OPTIMAL study prospectively showed the importance of pre-discharge echo for hospitalized HF patients. Careful attention is needed regarding the haemodynamic status of HF patients by administering pre-discharge echo to avoid HF re-hospitalization after discharge, and pre-discharge echo may provide additional information for deciding the appropriate discharge time. Our findings may thus offer a new insight into the management of hospitalized HF patients.

Novel noninvasive estimation of mixed venous oxygen saturation by echocardiography and expired gas analysis.

Mixed venous oxygen (O2) saturation ([Formula: see text]) is an important measure for evaluating the sufficiency of cardiac output (CO) relative to whole body O2 consumption (V̇o2), while clinical use is limited to the required invasive catheterization. According to Fick's equation, V̇o2 (mL/min) = CO (L/min) × Hb (g/dL) × 1.36 (mL/g) × ([Formula: see text] - [Formula: see text])/10 (Hb = hemoglobin concentration, [Formula: see text] = arterial blood O2 saturation). Because V̇o2, CO, Hb, and [Formula: see text] can be measured noninvasively with expired gas analysis, echocardiography, a simple blood test, and percutaneous O2 saturation, respectively, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. In 47 patients (29 men; mean age, 70 ± 12 yr) who underwent right heart catheterization, [Formula: see text] was directly measured by sampling pulmonary artery blood. Noninvasively calculated [Formula: see text] was also obtained by the method described above. The calculated [Formula: see text] was significantly correlated with the measured [Formula: see text] (r = 0.79, P < 0.001) and was significantly smaller than the measured [Formula: see text] (70 ± 5.1 vs. 72.1 ± 4.9%, P < 0.001). Bias at [Formula: see text] was -2.2% (95% confidence interval, -3.2 to -1.1%) with limits of agreement from -9.5 to 5.2%, demonstrating acceptable agreement. The optimal cutoff value of calculated [Formula: see text] was 69% for reduced measured [Formula: see text] < 70% with an area under the curve of 0.94. Reduced calculated [Formula: see text] < 69% indicated a sensitivity of 92.9% and a specificity of 90.9% for reduced measured [Formula: see text] < 70%. Noninvasive [Formula: see text] calculated from echocardiography, expired gas analysis, percutaneous arterial blood O2 saturation, and hemoglobin level significantly correlated and agreed well with direct [Formula: see text] measured by catheterization. This novel method allows for practical evaluation of [Formula: see text] to assess the sufficiency of CO according to whole body metabolism.NEW & NOTEWORTHY Clinical use of mixed venous oxygen saturation ([Formula: see text]) is limited to the required invasive procedure. With Fick's equation, expired gas analysis, echocardiography, simple blood tests, and percutaneous oxygen saturation, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. The present study examined the relationship between measured [Formula: see text] and calculated [Formula: see text] in patients who underwent right heart catheterization and demonstrated acceptable agreement. This novel method can expand the indication of evaluating [Formula: see text].

Importance of Nonlongitudinal Motion Components in Right Ventricular Function: Three-Dimensional Echocardiographic Study in Healthy Volunteers.

BACKGROUND: Global right ventricular (RV) function is determined by the interplay of different motion components related to the myofiber architecture, and the relative importance of these components is still not thoroughly characterized. The aims of this study were to quantify the relative contributions of longitudinal, radial, and anteroposterior motion components to global RV function and to examine their determining factors in a large cohort of healthy volunteers using three-dimensional echocardiography. METHODS: Three hundred healthy adults with a balanced age range and an equal sex distribution were investigated at two centers. A three-dimensional mesh model of the right ventricle was generated, and its motion was decomposed along the three anatomically relevant axes. Multiplicative relative contributions were measured by dividing the ejection fraction (EF) values generated by shortening in the longitudinal, radial, and anteroposterior directions by global RV EF (longitudinal EF index [LEFi], radial EF index [REFi], and anteroposterior EF index, respectively). The circumferential contribution was defined as shortening in the radial and anteroposterior directions, omitting only longitudinal shortening. RESULTS: Circumferential EF index was markedly higher compared with LEFi (79 ± 7% vs 47 ± 9%, P < .001). LEFi (47 ± 9%) and anteroposterior EF index (49 ± 7%) were found to be similar in the pooled population, whereas REFi (44 ± 10%) was lower (P < .001). In younger individuals (20-39 years of age), the relative contribution of longitudinal shortening was significantly higher compared with the radial component; however, in the older age groups, LEFi and REFi were comparable. Age, body surface area, heart rate, and RV end-diastolic volume were independent predictors of LEFi and REFi, but all with opposite effects on the two motion directions. CONCLUSIONS: In contrast to the traditional viewpoint, the contributions of the radial and anteroposterior motion directions may be of comparable significance with that of longitudinal shortening in determining global RV function. Standard parameters referring only to longitudinal shortening of the right ventricle may be inadequate to characterize RV function thoroughly.