3D Echocardiography Research Articles

FEBio FINESSE: An Open-Source Finite Element Simulation Approach to Estimate In Vivo Heart Valve Strains Using Shape Enforcement.

Finite element simulations are an enticing tool to evaluate heart valve function; however, patient-specific simulations derived from 3D echocardiography are hampered by several technical challenges. The objective of this work is to develop an open-source method to enforce matching between finite element simulations and in vivo image-derived heart valve geometry in the absence of patient-specific material properties, leaflet thickness, and chordae tendineae structures. We evaluate FEBio Finite Element Simulations with Shape Enforcement (FINESSE) using three synthetic test cases considering a range of model complexity. FINESSE is then used to estimate the in vivo valve behavior and leaflet strains for three pediatric patients. Our results suggest that FINESSE can be used to enforce finite element simulations to match an image-derived surface and estimate the first principal leaflet strains within strain. Key considerations include: (i) defining the user-defined penalty, (ii) omitting the leaflet commissures to improve simulation convergence, and (iii) emulating the chordae tendineae behavior via prescribed leaflet free edge motion or a chordae emulating force. In all patient-specific cases, FINESSE matched the target surface with median errors of approximately the smallest voxel dimension. Further analysis revealed valve-specific findings, such as the tricuspid valve leaflet strains of a 2-day old patient with HLHS being larger than those of two 13-year old patients. FEBio FINESSE can be used to estimate patient-specific in vivo heart valve leaflet strains. The development of this open-source pipeline will enable future studies to begin linking in vivo leaflet mechanics with patient outcomes.

Different right ventricular mechanics in atrial and ventricular secondary tricuspid regurgitation and their prognostic role. A multicentric three-dimensional echocardiography study

Abstract Background/Introduction Secondary tricuspid regurgitation (STR) can develop from markedly different etiologies. Both progressive dilation and dysfunction of the right atrium (atrial phenotype, ASTR), and adverse right ventricular (RV) remodeling (ventricular phenotype, VSTR) may result in STR. RV function is a major determinant of outcome in patients with STR. However, data about how RV function adapts to ASTR and VSTR are scarce, and the prognostic implications of RV mechanics in ASTR and VSTR remain to be clarified. Purpose Accordingly, we aimed to investigate the RV mechanical patterns in ASTR and VSTR and to examine their prognostic role using three-dimensional (3D) echocardiography. Methods We enrolled 192 patients with STR (60% women) who underwent clinically indicated transthoracic echocardiography in a multicentric prospective observational study. The primary outcome was defined as a composite of heart failure hospitalization or cardiac death. STR etiology was assessed based on the TVARC criteria (ventricular STR n=134, atrial STR n=58). STR severity was categorized using STR effective regurgitant orifice area according to current guidelines. We assessed RV function by measuring the tricuspid annular plane systolic excursion (TAPSE) by M-mode echocardiography and RV ejection fraction (EF) by 3D echocardiography. In addition, we imported the 3D RV meshes into the ReVISION software package (Argus Cognitive, Inc, Lebanon, USA) to quantify the relative contribution of the longitudinal (LEFi), radial (REFi), and anteroposterior motion components (AEFi) to total RV EF. Results ASTR and VSTR patients had comparable TAPSE (17±5 mm vs. 18±5 mm, p=0.10), while RV EF was significantly higher in ASTR (54±7% vs. 47±10% p<0.001). Although LEFi (0.37±0.08 vs. 0.38±0.10, p=0.95) and AEFi (0.45±0.08 vs. 0.44±0.11, p=0.53) were comparable between ASTR and VSTR, REFi was significantly lower in VSTR (0.52±0.09 vs. 0.47±0.12, p<0.01). RF EF was comparable among STR severity grades (mild vs. moderate vs. severe: 50±11 vs. 49±9 vs. 50±10%, respectively, p=0.85). Conversely, LEFi was significantly higher in mild and moderate STR vs severe STR (0.39±0.08 vs. 0.39±0.09 vs. 0.35±0.10, respectively, p=0.04). Using multivariable Cox regression based on variables significant in the univariate analysis, REFi was a significant independent predictor of outcome in the entire cohort (hazard ratio: 0.978 [CI, 0.959-0.999], p= 0.037). Conclusions Using 3D echocardiographic assessment, ASTR and VSTR patients demonstrated significant differences in the RV mechanical pattern, with a lower contribution of the radial contraction in the case of ventricular STR etiology. While RV EF was comparable between STR severity grades, the relative importance of the longitudinal motion significantly differed. Notably, the relative contribution of radial motion to RV function demonstrated independent prognostic value in patients with STR.RV mechanics in STR severity stages

Sex-specific prognosis of right ventricular size measured by 3D echocardiography following isolated tricuspid valve surgery

Abstract Backgrounds Isolated tricuspid valve surgery (ITVS) is considered a high-risk procedure. Right ventricular (RV) size plays a critical role in the prognosis of ITVS patients. The effect of sex differences in the degree of right ventricular（RV）dilatation in ITVS patients has not been established. Purpose The primary objective of this study was to assess in-hospital major adverse events (AEs) following ITVS in women compared with men on the basis of preoperative RV size measured by 3D echocardiography. Methods Consecutive patients undergoing ITVS were identified from a prospectively maintained database.Transthoracic echocardiography was performed the day before ITVS. In-hospital AEs were defined as one of the following occurring before discharge: death, shock, acute renal failure requiring dialysis, or prolonged (>72h) mechanical ventilation. 3D RV parameters including end-diastolic volume (EDV), end-systolic volume (ESV), EDVi (indexed by body surface area), ESVi (indexed by body surface area) and ejection fraction (EF) were calculated using commercially available software. Comparison of the adjusted odds ratios (ORs) generated by multivariate logistic regression of in-hospital AEs between women and men on the basis of baseline RV parameters. Results 59 patients (median age 62 years, 42.37% male, functional tricuspid regurgitation in 62.71%) were finally enrolled. In-hospital AEs were identified in 23 patients (3 death, 5 shock, 5 renal failure, 10 prolonged mechanical ventilation). The risk of AEs was increased from baseline, when the ESV was 69.73 mL for women and 90.66 mL for men. Regarding EDV, the risk for women increased at 130.49 mL compared with 170.36 mL in men. Accordingly, when indexed by body surface area, women had a lower inflection point for both EDVi and ESVi (76.71 mL/m2 vs 91.35 mL/m2, 34.04 mL/m2 vs 52.49 mL/m2). However, there was no inflection point for increased risk with RVEF in either men or women. Conclusion Women undergoing ITVS have a higher risk of in-hospital AEs with smaller RV size. These results support the use of sex-specific thresholds for RV size when making surgical decisions in patients with severe tricuspid regurgitation.Figure 1.Adjusted ORs for RV size.

Multi-vendor validation of automated left ventricular analysis from 3D echocardiography using artificial intelligence

Abstract Background Accurate echocardiographic assessment of left ventricular (LV) function is dependent on both image acquisition and analysis. Although 3D echocardiography (3DE) is increasingly recommended for volume quantification, manually derived volumes are limited by operator subjectivity, variable image quality, and the lengthy duration of analysis. Consequently, several automated approaches based on artificial intelligence (AI) have been proposed to segment the LV cavity from 3DE and have demonstrated better accuracy and reproducibility compared to human experts. While the utility of AI models in the clinic depends on their ability to generalise to different populations and ultrasound vendors, the external validation of developed models remains limited. Purpose This study evaluates the ability of an existing AI model trained using data from a single vendor to accurately estimate routine 3DE LV indices in an independent external dataset acquired using equipment from a different vendor. Methods A previously published and internally validated deep learning model for segmentation of the LV cavity and myocardium from 3DE was used to automatically derive LV indices including end-diastolic volume (EDV), end-systolic volume (ESV), LV mass, and ejection fraction (EF) [1]. A second independent dataset consisting of paired 3DE and CMR images from 65 marathon runners from a different centre (using equipment from a different vendor) was subsequently used for external validation. Images from both datasets were subjectively scored from 1 (poor) to 5 (excellent) as a measure of image quality. Agreement with CMR as the reference was assessed using a two-way mixed effects intraclass correlation coefficient (ICC), supplemented by Bland-Altman analysis, to determine the model bias (between 3DE and CMR) and 95% limits of agreement (LOA). To assess whether performance could be improved by inclusion of multi-vendor data during training, the initial model was fine-tuned using a small subset (n=9) of images from the second centre. Results The mean image quality score from the second dataset was 2.5 (± 1.1), which was significantly lower than the mean of 3.4 (± 1.0) from the first dataset. Despite vendor and image quality differences, the initial model produced good agreement with CMR in EDV, ESV, and LV mass but only poor agreement in EF (Fig 1). Fine tuning greatly improved agreement in EF with reduced bias and narrower 95% LOA (Fig 2). Conclusion With the addition of a small number of cases for fine-tuning, AI models for automated LV analysis can achieve good performance analysing 3DE images acquired from a different vendor and population. Advancing model generalisability through more sophisticated data augmentation strategies may enable truly vendor-agnostic automated LV analysis from 3DE.

Combined 3D left ventricular-arterial coupling and 3D left atrial-ventricular coupling indices could better predict MACE in young patients with STEMI

Abstract Background Left ventricular arterial coupling index (VAC) proved to be a key determinant of cardiovascular performance. Previous trials also emphasized the prognostic value of left atrial-ventricular coupling index (LACI) that was independently associated with cardiovascular death and all-cause mortality. Both indices have been associated with disease severity and adverse outcomes. Purpose We aimed to evaluate the prognostic role of 3D VAC, 3D LACI and their combination assessed by 3D echocardiography in a cohort of young patients with STEMI. Patients and methods In this prospective study we enrolled 76 young consecutive patients (under 50 years old) with STEMI treated by primary PCI who underwent both 2D and 3D echocardiography. 3D VAC was calculated as the ratio between arterial elastance (EA) and end-systolic left ventricular elastance (EES), based on a formula proposed by Chen. 3D LACI was determined as the ratio between 3D left atrial end-diastolic volume (minimal atrial volume) and 3D left ventricular end-diastolic volume. Patients were followed up for one year after STEMI and the primary endpoint was the occurrence of MACE defined as death from cardiovascular causes, heart failure requiring hospital admission, or repeat revascularisation. Results Out of 76 patients, 15.8% had an adverse event during the 12 months follow up period. We divided the patients in two groups according to the presence or absence of MACE. Patients with MACE had higher VAC (2.15±0.62 vs. 1.25±0.29%, p<0.0001) and higher LACI (25.1±7.17% vs. 18.3±6.58%, p=0.002). In ROC analysis VAC and LACI combined had the best AUC for MACE prediction (AUC 0.961, p<0.0001), followed by VAC (AUC 0.922, P<0.0001), and then, LACI (AUC 0.772, P<0.001). For each variable we determined a cut off value. A value over 1.7 for VAC and 23.83% for LACI can predict unfavourable outcome with 83.3% sensitivity and 97.1% specificity for VAC and 67% sensitivity and 80% specificity for LACI. In both univariate and multivariate COX regression analysis, both VAC and LACI remained independent predictors for MACE. Moreover, their combination proved to have better predictive value for adverse events compared to each taken separately. We divided the study population into 4 groups: Group 1: VAC < 1.7 and LACI < 23.83%. Group 2: VAC <1.7 and LACI > 23.83%. Group 3: VAC > 1.7 and LACI < 23.83% and Group 4: VAC > 1.7 and LACI >0.23.83%. Kaplan Meier analysis shows significant differences among groups (log rank χ2 = 35.48, p < 0.0001). Calculation of Kaplan-Meier curves for the four groups indicated that the combination of the VAC > 1.7 and LACI > 23.83% had the strongest predictive power for MACE. Conclusion In conclusion 3D VAC and 3D LACI combined are better at predicting adverse events than each variable taken separately and could be used for a more accurate risk stratification in young patients with STEMI.

Left atrial volumetric-mechanical coupling index as a marker of subclinical primary heart involvement in systemic sclerosis

Abstract Background Primary heart involvement in systemic sclerosis (SSc) is a common yet often clinically silent marker of poor prognosis. Up to 80% of patients have histopathological evidence of heart involvement, highlighting the need for better screening and diagnostic methods. N-terminal pro-brain natriuretic peptide (NTproBNP), a well-established cardiac biomarker, is often increased in patients with SSc, but with a not fully understood mechanism. Meanwhile, left atrial volumetric-mechanical coupling index (LACI), a new echocardiographic parameter, has been shown to predict cardiovascular outcomes in heart failure patients and the general population, but it has not been studied in SSc. Purpose To identify new echocardiographic parameters, particularly related to left atrial volume and function, as markers of increased NTproBNP in SSc patients without overt heart involvement. Methods Consecutive SSc patients without overt heart disease referred for routine cardiac screening underwent 2D and 3D transthoracic echocardiography, including atrial and ventricular strain analysis. LACI was calculated by both 2D and 3D echocardiography as the ratio between the left atrial volume index and the tissue-Doppler-imaging septal a’ velocity. Patients with significant structural and functional changes suggestive of systolic or diastolic dysfunction or pulmonary hypertension, and those with impaired global left ventricular strain were excluded. Logistic regression, Pearson correlation coefficients, and area under the receiver-operating characteristic curve (AUC) are used to analyze the association and predictive power of LACI for elevated NTproBNP. Results A total of 36 SSc patients (55±10 years old; 34 (94%) women; mean disease duration 14±11 years) were included. Sixteen (44.4%) had diffuse cutaneous involvement (dcSSc). Seventeen (47%) patients had increased NTproBNP levels (i.e. >125 pg/mL). Among all tested variables, 3D LACI had the best correlation with NTproBNP values (r = 0.63, p<0.001). A 3D LACI of >2 associated with NTproBNP of >125 pg/mL (odds ratio 7.33 [95%CI 1.38-38.8]; p=0.01) and predicted these increased values with a sensitivity of 76.9% and a specificity of 81.2% (AUC 0.78). NTproBNP was also correlated with 2D LACI (r=0.55, p<0.001), peak left atrial longitudinal strain (r=-0.42, p=0.01), and left atrial contraction strain (r=0.48, p=0.005). Compared to patients with limited cutaneous involvement, those with dcSSc had higher NTproBNP values (250±139.6 vs 107.2±110.9 pg/mL, p=0.001), higher 3D LACI values (2.6±0.9 vs 1.9±0.5, p=0.02), with similar left atrial and ventricular strain parameters. Conclusion Left atrial volumetric-mechanical coupling index assessed by 3D echocardiography is significantly associated with and predictive of elevated NTproBNP levels in SSc patients without overt heart disease and may be a potentially useful non-invasive marker for screening for early subclinical heart involvement in SSc patients.

Beyond 2D echocardiography: A novel multiparametric assessment of right ventricular dysfunction in transcatheter tricuspid valve repair

Abstract Background Patients with severe tricuspid regurgitation (TR) are heterogenous and complex in terms of etiology, comorbidities and state of disease. Right ventricular (RV) function measured by RV to pulmonary artery coupling (RVPAc) is prognostic in transcatheter tricuspid valve repair (T-TEER). However, traditional 2D echocardiographic measures have critical limitations and RVPAc fails to respect the degree of volume overload/dilation of the RV, which is a key clinical tracer for right ventricular dysfunction (RVD). Purpose We aimed to refine RVPAc by incorporating RV dilation, assessed by 3D echocardiography, to improve the assessment of RV dysfunction for an enhanced outcomeprediction in T-TEER patients. Methods We analyzed 262 patients undergoing T-TEER with complete 3D echocardiography. Results Despite similar RV function across groups, RV dilation (HR 1.85; 1.10, 3.12; p=0.020) and impaired RV free wall longitudinal strain (RVFWLS, HR 1.73, 1.02, 2.92, p=0.042) predicted increased 1-year mortality. A novel RVPAc parameter [RVFWLS/(3D-RVEDV*sPAPinvasive)] was developed, associating RVPA-Uncoupling with a tripled risk of death (HR 3.19, 1.7-6.0, p<0.001). NYHA Class IV and the new RVPAc were independent mortality predictors after T-TEER, with the modified RVPAc showing superior predictive value over traditional RVPAc (c-index 0.68 vs. 0.57, p=0.027). Conclusion The novel RVPAc parameter, integrating RV dilation and function, is a powerful predictor of survival post-T-TEER, underscoring the importance of timely intervention in severe TR and RVD. 3D echocardiography plays a critical role in assessing RV dimension and function, with implications for the management and prognosis of TR patients.Central Figure

Preliminary findings of the TB-HEART Study: prevalence of cardiac pathology among newly diagnosed patients with tuberculosis with and without HIV in Zambia

Abstract Background Cardiovascular diseases (CVD) burden is rapidly increasing in sub-Saharan Africa (SSA) where tuberculosis and HIV prevalence remain high.(1-3) Recent data suggest pulmonary tuberculosis (PTB) is associated with increased CVD morbidity.(4) However, the mechanisms of cardiac injury remain poorly understood. Purpose The TB-HEART study is a cross-sectional and natural history study consecutively recruiting participants with newly-diagnosed PTB, living with and without HIV in Zambia. The primary outcome is the burden of cardiac pathology in PTB patients with and without HIV. Methods Participants with bacteriologically-proven PTB, consecutively recruited from an outpatient settings in Zambia, undergo detailed clinical and functional assessments including point-of-care and standard two-dimensional (2D) echocardiography. Participants are reviewed at completion of TB treatment when all assessments are repeated. The target sample size is 250 participants with PTB, with and without HIV, matched 2: 1 to participants without PTB, stratified by HIV. Results Since 1 November 2023, we have recruited 73 participants with a mean age of 35.3±10.9 years of whom 51/73 (69.9%) are male and 19/73 (23.5%) are living with HIV. Baseline characteristics including cardiovascular risk factors, TB symptoms, anthropometry and clinical and functional observations at presentation, stratified by HIV status, are summarised in Table 1. We detected significant cardiac pathology (defined as left ventricular ejection fraction (LVEF) <51% and/or pericardial effusion >2cm in depth) in 8/65 (12.3%) participants for whom 2D-echocardiography had been completed. Median LVEF was 61.2% (IQR 57.7-67.8). LVEF was normal in 59/65 (91%); mildly abnormal in 5/65 (7.7%); and moderately abnormal in 1/65 (1.5%) participants, respectively. Pericardial effusion >0.5cm was detected in 16/65 (24.6% ) participants and maximum effusion depth was >2cm in 2/16 (3.1%), 1-2cm in 12/16 (75%) and <1cm in 2/16 (12.5%). 2D-echocardiography findings, stratified by HIV-status, are described in Table 2 alongside two echocardiography stills of typical pericardial effusion findings in one participant. Conclusions Our preliminary results demonstrate a higher than expected prevalence of cardiac pathology among participants with PTB with and without HIV, which ranges from 1-7% in autopsy studies and case series.(5-7) The most common cardiac pathology was pericardial effusion. Further analyses will include cardiac biomarkers; repeat clinical and echocardiographic assessments at TB treatment completion; and comparator data, to determine associations between prevalent cardiac pathology and PTB controlling for HIV and TB status, respectively. This may have important implications for clinical practice to prevent complications such as constrictive pericarditis; and policy design to better integrate TB and HIV patient services with preventative care to reduce future CVD risk.Table 1 - Baseline characteristicsFigure 1 and Table 2

Global longitudinal strain measurement in the modern era - is artificial intelligence the answer ?

Abstract Background Global longitudinal strain (GLS) enhances the assessment of left ventricular (LV) function beyond ejection fraction (EF) in 2D echocardiography (Echo). However, manual GLS measurement, the most common technique, is operator dependent. A novel vendor-independent artificial intelligence (AI)-based software streamlines automated 2D-Echo exam evaluation and GLS calculation. Purpose We sought to evaluate the ability of the AI to automatically identify LV 4-, 2-, and 3-chamber views (CV) from 2D-Echo exams and to validate GLS against the conventional manual method. Methods 540 patients underwent standard 2D-Echo exams. The server-based AI recognized the optimal LV CVs from 2D-Echo exams and automatically calculated triplane GLS by endocardial delineation (n=489, 91%). Manual LV GLS was performed independently by accredited cardiologists. Pearson’s correlation (R) and Bland-Altman analysis were performed to assess bias and limits of agreement (LOA) for GLS. Multivariate between-method regression was performed using ordinary least squares to disclose possible sources of possible bias. Significance was defined as a 2-tailed P value < 0.05. Results Patients’ median age was 70 years [18-93], 59% were males. The 2D-Echo indications were coronary artery disease (36%), valvular heart disease (15%), non-ischemic heart failure (15%) and others (34%). The feasibility of the AI to calculate GLS was 91% (n=489) due to endocardial border delineation issues. AI correctly classified all CVs. An excellent correlation (r=0.92, p<0.001) was observed between AI and manual GLS, with low bias (0.5%) and narrow LOAs (-3.1 and +4.2%) (Figure 1, top row). We identified LV end-diastolic volume and EF as statistically significant confounders (p < 0.05) with only small effect as depicted in Figure 1 (bottom row). Neither sex, age, acoustic window, body mass index, nor heart rate, along with the interaction with sex, end-diastolic volume, or EF, were significant (p > 0.23). Conclusion AI-based LV GLS calculation in 2D-Echo shows promising feasibility and accuracy. Strong agreement between AI-derived GLS and manual measurements supports its reliability. The AI's ability to identify optimal LV views underscores its robustness. Further validation and refinement are warranted, highlighting the transformative potential of AI in advancing cardiovascular diagnostics.

Mortality and heart failure in patients with severe tricuspid regurgitation. Impact of RV volumes and function by CMR.

Abstract Background Beyond symptoms, right ventricle (RV) dilatation and dysfunction are established criteria for intervention in patients with significant tricuspid regurgitation (TR); however defined thresholds to support intervention are lacking. As a result, the optimal timing for intervention remains controversial and it is commonly undertaken at a late stage. Purpose To describe prognostic cut-off values of RV size and function by Cardiac Magnetic Resonance in a multicentre cohort of patients with at least severe TR. Methods The study enrolled patients with at least severe TR assessed by 2D echocardiography who underwent a contemporary cardiac magnetic resonance (CMR) study. Conventional parameters of biventricular volume and function were assessed in all patients. A combined endpoint of hospital admission due to heart failure (HF) and all-cause mortality was defined. Results 318 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (70 ± 11 years, 67% female, 73% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. After a median follow-up of 28 months (IQR: 10-54 months), 42% of the patients (n=134) experienced the combined endpoint (n=113 were admitted due to HF, n=61 died). After adjusting for age, NYHA class, comorbidities, type of TR and LVEF in a multivariate Cox proportional model (LR Chi-Square: 88.01, p<0.001), RV-EDV and RVEF were independently associated with all-cause mortality and heart failure (adjusted HR for RV-EDV per ml/m2 =1.008 [1.005-1.012], p<0.001 and RVEF HR per 1%=0.961 [0.942-0.981], p<0.001). Thresholds of RV-EDV ≥ 93 ml/m2, RV-ESV ≥ 39 ml/m2 and RVEF ≤ 58% held the best accuracy to predict outcomes (figure). In multivariable analysis, prognostic cut-off values of RV-EDV, RV-ESV and RVEF was associated with 1.91, 2.03, and 1.76-fold increased risk of HF or all-cause mortality respectively (RV-EDV HR: 1.91 [1.34-2.71], p<0.001, RV-ESV HR 2.03 [1.42-2.89], p<0.001 and RVEF HR1.76 [1.25-2.49], p=0.001). Conclusion RV size and function are crucial for determining optimal timing for TR intervention. CMR remains the gold standard to assess RV remodeling. Cut-off values of RV volume and function by CMR are defined in a multicentre cohort of patients based on outcome data; proposed thresholds differ from those previously established by echocardiography.Kaplan Meier curves

Gender-specific differences in severe tricuspid regurgitation. Finding from a TR multicentre CMR registry

Abstract Background Observational studies have suggested that severe tricuspid regurgitation (TR) is more prevalent in women than in men, although the pathophysiological causes that justify this difference are unknown. Purpose 1) to assess clinical and imaging differences by Cardiac Magnetic Resonance (CMR) between men and women and 2) to examine the relationship between gender and all-cause mortality in a multicentre cohort of patients with at least severe TR. Methods The study-enrolled patients with at least severe TR assessed by 2D echocardiography who underwent a contemporary cardiac magnetic resonance (CMR) study. The primary outcome was all-cause mortality. Results 318 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (70 ± 11 years, 67% female, 73% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. Women showed a non-significant tend to lower prevalence of comorbidities, lower BNP and significantly lower creatinine values (table). Regarding CMR variables, women showed smaller indexed right ventricle (RV) volumes higher RVEF and lower TR regurgitant volume (table, p<0.05 for all). Left ventricle (LV) volumes were smaller and LVEF higher in women compared to men (p<0.001). During a median follow-up of 28 months (IQR: 10-54 months), there were 61 deaths (19%) with an estimated 5-year survival of 74%. Cumulative all-cause mortality was significantly worse in men compared to women (27% vs. 15%, p<0.001, figure). Male gender was significantly associated with all-cause mortality independently of age, RV volumes, RVEF and LVEF (HR 2,2 [1.34-3,68], p =0.002). Different cut-off values of index RV volumes and EF were predictive of mortality in men and women. In men a RV-EDV >110 ml/m2 and RVEF<57%; in women a RV-EDV >90 ml/m2 and RVEF< 60% were predictive of all-cause mortality (p<0.01). Conclusion Severe TR is more prevalent in women; however, it shows lower RV remodeling, better RV function and lower rate of events compared to men. Different prognostic RV cut-off values are provided based on CMR data.Gender differencesKaplan Meier Curves

Effective RV ejection fraction by CMR: a new index of RV function in patients with severe TR

Abstract Background Right ventricle (RV) dysfunction represent an formal indication for intervention in patients with significant tricuspid regurgitation (TR). RV ejection fraction (RVEF) by Cardiac Magnetic Resonance (CMR) is considered the gold standard of RV function; however it is influenced by changes of preload conditions and may remain unaffected until late stages in severe TR. Effective RV ejection fraction (eRVEF) is corrected by the amount of TR and may reflect an earlier parameter of RV dysfunction. Purpose To compare the prognostic impact of both indices of RV function: RVEF and eRVEF in a multicentre cohort of patients with severe TR. Methods Patients with at least severe TR assessed by 2D echocardiography with a contemporary cardiac magnetic resonance (CMR) study were included in this study. In addition to conventional parameters of biventricular volume and function, eRVEF was assessed in all patients. eRVEF was calculated according to the formula: eRVEF=net pulmonary forwardflow/RV− EDV (figure). A combined endpoint of hospital admission due to right heart failure and cardiovascular mortality was defined. Results 271 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (age 71 ± 11 years, 67% female, 83% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. After a median follow-up of 27 months (IQR: 10-53 months), 41% of the patients (n=112) experienced the combined endpoint (n=97 were admitted due to HF, n=49 died). After adjusting for age, NYHA class, comorbidities, type of TR and LVEF in multivariate Cox proportional models, both RVEF and eRVEF were independently associated with all-cause mortality and heart failure (adj HR for RVEF HR per 1%=0.96 [0.94-0.98], p<0.001 and for eRVEF per 1%=0.98 [0.96-0.99], p<0.001). A value of eRVEF of ≤37% were associated with impaired prognosis (figure). eRVEF identified higher rates of RV dysfunction compared to RVEF (49% vs 38%, p<0.001). eRVEF was superior to RVEF to predict outcomes (higher AUC 0.70 [0.63-0.76] vs 0.66 [0.59-0.73, p<0.001; Δ C-statistic 0.139 [0.040-0.237], p=0.05). Conclusion RV function is crucial for determining optimal timing for TR intervention. eRVEF is corrected by the amount of TR and identify higher rates of RV dysfunction in severe TR. eRVEF held stronger association with outcome compared to RVEF.eRVEF calculationKaplan Meier Curves

Three dimensional biatrial expansion index as an independent predictor of outcome in dilated cardiomyopathy

Abstract Background Left atrial expansion index (LAEI) is a marker of left ventricular (LV) diastolic dysfunction and an outcome predictor in heart failure (HF). However, the role of the right atrial expansion index (RAEI) in the setting of left-sided HF is incompletely understood. Purpose We sought to evaluate the left, right and combined bi-atrial expansion index (BAEI) with three-dimensional (3D) echocardiography in a cohort of patients with dilated cardiomyopathy (DCM) and to assess their prognostic role. Methods We enrolled 121 consecutive patients (mean age 59±14 years, 74% men) with DCM in sinus rhythm, who underwent 3D echocardiography and were prospectively followed for 19±11 months for an endpoint of death, nonfatal cardiac arrest and HF hospitalization. As previously described, for the left atrium (LA), LAEI was measured as (3D LA Vmax – 3D LA Vmin) x 100/3D LA Vmin, where Vmax was the maximal end-systolic atrial volume and Vmin was the minimal end-diastolic atrial volume. For the right atrium (RA), RAEI was calculated as (3D RA Vmax – 3D RA Vmin) x 100/3D RA Vmin. BAEI was defined as the sum of LAEI and RAEI. Results 55 patients (46%) reached the endpoint: there were 27 deaths, 5 nonfatal cardiac arrests and 23 readmissions for HF. Patients with adverse outcome had lower LAEI (52±25 vs. 63±36, p=0.047), lower RAEI (57±29 vs. 70±32, p=0.02), lower BAEI (108±46 vs. 133±55, p=0.008). In univariate Cox regression, all three expansion indices were predictors of adverse events: HR=3.23 [95% CI, 1.45-7.20], p=0.004 for LAEI, HR=2.12 [95% CI, 1.24-3.61], p=0.006 for RAEI, HR=3.99 [95% CI, 1.70-9.36], p=0.001 for BAEI. We constructed a multivariable model with well-established event predictors in DCM and one expansion index at a time. After adjustment for age, left ventricular ejection fraction, mitral regurgitation severity and pulmonary artery systolic pressure, all three expansion indices remained independent predictors of the composite endpoint: HR=2.75 [95% CI, 1.18-6.38], p=0.02 for LAEI, HR=1.86 [95% CI, 1.04-3.31], p=0.04 for RAEI, HR=3.53 [95% CI, 1.46-8.51], p=0.005 for BAEI. BAEI yielded the highest incremental prognostic power (likelihood ratio chi2 test=14, p=0.03) on top of the baseline model consisting of age, left ventricular ejection fraction, mitral regurgitation severity and pulmonary artery systolic pressure (likelihood ratio chi2 test=9). Conclusion In DCM, 3D atrial expansion indices are significantly lower in patients with major adverse events, reflecting a more impaired atrial reservoir dysfunction. Both LAEI, RAEI and BAEI were independent outcome predictors in patients with DCM. Combining the left and right atrial expansion indices might improve risk stratification, since BAEI had the highest predictive value after adjustment for confounders.

Predictive factors for recurrent tricuspid regurgitation after tricuspid annuloplasty: 3D echocardiography study

Abstract Introduction There is growing concern about the recurrence of tricuspid regurgitation (TR) after tricuspid annuloplasty (TA) in individuals with functional tricuspid regurgitation (FTR). While TA is effective in treating FTR, a comprehensive understanding of the echocardiographic factors influencing TR recurrence is crucial. Aim This study aims to employ multivariate regression analysis to investigate the prognostic significance of tricuspid valve (TV) geometry and echocardiographic parameters associated with both RV geometry and function. The focus is on comprehending these relationships in the context of recurrent TR subsequent to TA. Methods This prospective observational cohort study aimed to explore factors contributing to recurrent tricuspid regurgitation (TR) after tricuspid annuloplasty (TA). The focus was on patients with moderate or severe functional TR due to left heart valvular disease, particularly severe mitral regurgitation, excluding those with ischemic heart disease. The cohort included 66 individuals undergoing preoperative assessments with 2D and 3D echocardiography, quantifying RV and right atrial (RA) geometry, functional, and tricuspid valve (TV) parameters. TR severity followed ESC guidelines. Patients were categorized into effective TA (50 patients) and recurrent TR (16 patients) groups, defined by mild-moderate TR and significant moderate-severe TR one year post-surgery, respectively. SPSS software facilitated statistical analysis, with adjusted logistic regression considering parameters such as age and gender. Results Among the patients (54% male, mean age 68±9 years), no significant differences were found in gender, left ventricular and atrial parameters, or preoperative TV orifice area between groups (recurrent TR vs. effective TA: 38 [33] mm2 vs. 29 [15] mm2, p=0.117). Univariate logistic regression analysis identified Septal-Lateral Systolic TA Diameter (OR 1.62), Septal-Lateral Diastolic TA Diameter (OR 1.99), and Major Axis Diastolic TA Diameter (OR 1.59) as key predictors. For diagnostic efficacy, ROC analysis revealed Major Axis Diastolic TA Diameter (AUC 0.848; cut-off 52.5 mm), TV Leaflet Tenting Volume (AUC 0.778; cut-off 5.1 ml), and RV Basal Diameter (AUC 0.763; cut-off 47.5 mm) as the most predictive parameters. The combined use of predefined RV basal diameter and Major Axis Diastolic TA Diameter showed the highest odds ratio for recurrent TR. Conclusion Key predictors, including Septal-Lateral Systolic and Diastolic TA Diameters, and Major Axis Diastolic TA Diameter, were identified, emphasizing their significance in understanding TR recurrence after tricuspid annuloplasty. The combination of predefined RV basal diameter and Major Axis Diastolic TA Diameter showed the highest odds ratio for recurrent TR, offering valuable insights for clinical assessment and preventive strategies.

3D echocardiography and biomarkers for early diagnosis and prediction of chemotherapy induced right ventricular dysfunction in non-Hodgkin lymphoma patients

Abstract Background RCHOP (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisone) use in non-Hodgkin's lymphoma (NHL) is limited by the risk of cardiotoxicity. Although the prognostic value of right ventricular (RV) function in mortality and morbidity has been well established, its involvement in chemotherapy-induced cardiotoxicity remains unclear. Aim To define new parameters able to detect early RV cardiotoxicity. Methods 51 patients (22 men, 61±14 years) with NHL scheduled for RCHOP, with three dimensional (3D) left ventricular (LV) ejection fraction (EF) >50%, were assessed at baseline, after 3rd and 6th cycle for right ventricular (RV) parameters: 3D EF, two dimensional (2D) global longitudinal strain (GLS) and free wall LS (FWLS), peak systolic annular velocity (S’), tricuspid annulus systolic excursion (TAPSE) and fractional area change (FAC). Biomarkers (troponin I, NT-pro-BNP) were measured. Cardiotoxicity was defined as LVEF reduction below 50% or preserved LVEF with LV LS decrease more than 15% from baseline. Results 15 (29%) of patients developed LV cardiotoxicity (group 1) while 36 did not fulfill this criteria (group 2). There was a significant reduction of RVEF, GLS, and FWLS, but not of RV S’, FAC, and TAPSE, starting with the 3rd cycle, with greater changes in group 1 vs. group 2 (see Table). RVEF reduction correlated with changes of FWLS, GLS, RV S’, and troponin (r=0.612, r=0.513, r=0.362, r=-0.358, respectively; all p<0.05). Reduction of FWLS after the 3rd cycle was the best independent predictor for RVEF decrease after the 6th cycle (R²=0.433, p<0.0001). FWLS decrease with more than 26% predicted cardiotoxicity after the 6th cycle (sensitivity of 81%; specificity of 78%). Conclusion 3D EF, 2D systolic deformation, and troponin I are able to detect early chemotherapy-induced right ventricular cardiotoxicity, and to predict further decline of RVEF in NHL patients. Thus, routine follow-up of RV function, along with the LV function, should be assessed during and after chemotherapy.RV parameters and troponin during RCHOP

Prognostic preoperative factors for recurrence of tricuspid regurgitation following annuloplasty: examining the influence of 3d echocardiography

Abstract Introduction The increasing worry revolves around the reappearance of tricuspid regurgitation (TR) following tricuspid annuloplasty (TA) among individuals dealing with functional tricuspid regurgitation (FTR). Despite TA's efficacy as a treatment, a complete understanding of the echocardiographic elements influencing the recurrence of TR is pivotal. This knowledge holds the potential to guide the development of more robust preventive strategies, aiming to ease the incidence of recurrent TR after TA. Aim The aim of this study was to examine the prognostic value of tricuspid valve (TV) and echocardiographic parameters related to both right ventricular (RV) geometry and function. Specifically, our focus is on understanding these relationships in the context of recurrent TR following TA. Methods This prospective observational cohort study aimed to investigate determinants of recurrent TR post-surgical TV repair. The focus was on patients with moderate or severe functional TR related to left heart valvular disease, primarily severe mitral regurgitation, excluding those with ischemic heart disease. The study involved 66 participants, assessed preoperatively with 2D and 3D echocardiography, examining RV and right atrial (RA) geometry, functional, and TV parameters. TR severity followed ESC guidelines. Two groups were formed: effective TA group (50 patients) and recurrent TR group (16 patients), defined by mild to moderate TR and significant moderate-severe TR one year post-surgery, respectively. Statistical analysis employed SPSS software, with adjusted univariate logistic regression considering age and gender. Results Of the patients, 54% were male, with a mean age of 68±9 years. Echocardiography parameters in Table 1 showed no significant differences in gender, left ventricular, atrial geometrical, functional parameters, or preoperative effective regurgitant TV orifice area between groups (recurrent TR vs. effective TA: 38 [33] mm2 vs. 29 [15] mm2, p=0.117). Univariate logistic regression analysis highlighted RV and RA geometry, along with TV diameter, as predictors for recurrent TR. Notably, 3D TV geometrical parameters had prognostic significance, as confirmed by univariate adjusted logistic regression analysis. Functional RV parameters did not exhibit statistical significance in this analysis. Conclusion In conclusion, the recurrence of moderate-severe functional tricuspid regurgitation following tricuspid annuloplasty is linked to the tricuspid annulus size, as well as the geometry of the right atrium and right ventricle before surgery. Notably, no correlation was identified between the recurrence of TR and alterations in RV function.

Changes in mitral and tricuspid valve morphology after surgical repair of pectus excavatum

Abstract Background The effect of pectus excavatum (PE) on cardiac morphology and function has been reported previously. The right heart chamber size and cardiac output improved after the surgical correction of PE. However, the effect on the mitral and tricuspid valve has not been investigated. Purpose Our purpose was to investigate the morphological changes in the tricuspid and mitral valve after PE surgery. Methods We enrolled 25 patients who underwent Nuss surgery for PE repair. The inclusion criteria were 1) aged 15 years or older, 2) Haller Index of more than 5.0, and 3) transesophageal echocardiography (TEE) during PE surgery. We measured RV size and the sphericity index of tricuspid and mitral valve using 3D echocardiography before and after the elevation of the sternum. The sphericity index was calculated as the ratio of anterior-posterior (AP)/medial-lateral (ML) dimeter for the mitral valve (MV) and septal-lateral (SL) / AP dimeter for the tricuspid valve (TV). Results Mean age was 26±11 years, and 28% was female. The Haller index was 6.9 ± 2.8. All patients had normal left ventricular and right ventricular function evaluated with transthoracic echocardiography. The chamber diameter of the base and mid in RV increased after the elevation of the chest. The AP and SL dimeter were enlarged after the elevation of the chest in the TV, and the sphericity index of TV did not change. On the other hand, AP diameter increased but ML diameter was constant in the MV, and the sphericity index of MV increased after the elevation of the chest. Therefore, the annulus size was increased but the morphology was not changed in the TV. Unlike the TV, the morphology of MV annulus became close to circular from flat shape. In several patients, trivial mitral regurgitation was observed after elevation of chest, and possibly affected by the morphological change of the MV annulus. Conclusions The surgical repair for pectus excavatum effected not only right ventricular morphology but also on the tricuspid and mitral valve. The annulus change was different between the tricuspid and mitral valve.

Automated non-invasive quantification of myocardial work using 3D echocardiography and validation with invasive catheter measurements

Abstract Background Myocardial work is an emerging technique for the assessment of left ventricular (LV) performance. Using blood pressure as an afterload determinate offers further insight into LV mechanics than can be detected with load-sensitive parameters of ejection fraction or global longitudinal strain (GLS). Observational studies have signalled benefit in identifying vulnerable ventricles in cardiomyopathy, valvular, and coronary disease. While the reference standard for calculating myocardial work is through catheterisation, this is impractical for routine assessment. Currently, a vendor specific non-invasive index of myocardial work is commercially available, but requires subjective manual analysis and identification of valvular events. With increasing availability of 3D echocardiography (3DE) and automated analysis techniques, there is potential to derive more reproducible estimates of myocardial work. Purpose We sought to test whether global myocardial work could be accurately, non-invasively, and automatically estimated using 3DE, in combination with standard non-invasive clinical measurements. Methods Patients undergoing left heart catheterisation as part of routine care were prospectively recruited, and 3DE was performed within one hour of invasive LV pressure measurement. A validated deep learning model was used to automatically analyse the 3DE image volumes to produce GLS curves, from which a smaller number of features (principal components) were extracted. The invasive pressure traces were separated into cycles, which were each paired with the strain trace that had the minimal difference in R-R interval (and excluded if the relative R-R interval difference exceeded 25%). For each patient, an invasively-derived estimate of myocardial work was calculated as the area enclosed by the median pressure-strain (PS) loop. A multivariate regression model was used to relate a set of routine clinical parameters to the invasively-derived myocardial work, and subsequently assessed using leave-one-out cross-validation. Results A total of 131 out of 153 patients were included for analysis (2 excluded due to R-R interval mismatch, 20 excluded due to poor image or pressure trace quality), with basic demographics presented in Table I. The final parameter set consisted of 6 variables: systolic and diastolic brachial cuff pressures, peak GLS, R-R interval, and two strain curve principal components. When fit into a leave-one-out model, this resulted in a Pearson r-value of 0.86, demonstrating a very high correlation between predicted and invasively-derived myocardial work estimates, with a bias of 0 mmHg% and 95% limits of agreement (LOA) of ± 423 mmHg% (Figure 1). Conclusion This study demonstrates that fully automated and reliable estimates of myocardial work can be derived using 3DE and deep learning combined with routine clinical parameters. Automated and non-invasive approaches may facilitate increased clinical uptake of myocardial work assessment.

Mechanical wave velocities in acute myocardial infarction: an exploratory study using three-dimensional high frame rate echocardiography

Abstract Background Evaluation of cardiac function is crucial for management of patients with acute myocardial infarction (AMI). Recently, high frame rate (HFR) echocardiography has enabled identification of fast-propagating mechanical waves (MW) within the myocardium. These waves have the potential to offer unique insights into myocardial tissue properties, including edema and fibrosis. However, the potential of 3D HFR echocardiography to accurately quantify MW velocities and thereby assess myocardial stiffness in AMI patients remains unexplored. Purpose To assess the feasibility of a novel method for estimating MW velocities using 3D HFR echocardiography in patients with AMI compared to healthy controls. Methods Twenty patients with first time ST-elevation myocardial infarction were included within 48 hours after reperfusion therapy. We used a commercially available ultrasound scanner to acquire conventional 3D high-quality (~20 frames per second) acquisitions and subsequent 3D HFR recordings (~820 frames per second). The high-quality recording was used to extract a myocardial mask to define the region of interest in the HFR acquisition to detect the atrial kick wave and generate a comprehensive 3D map of MW propagation and velocities. We compared MW velocities between these patients and twenty age- and sex-matched healthy controls. Results MW velocities were successfully measured in 93% of participants (17 patients and 20 controls). Global MW velocities were significantly higher in AMI patients compared to healthy controls (2.1±0.6m/s vs. 1.5±0.2m/s, p<0.001). Territorial values, corresponding to the theoretical perfusion area of the three main coronary arteries, were significantly higher in infarct-related territories in patients when compared to same territories in controls for all coronary territories: Right coronary artery: 1.9±0.7 m/s vs. 1.4±0.3m/s, p<0.05; Circumflex artery: 3.1±1.5m/s vs. 1.7±0.4m/s, p<0.01; and Left anterior descending artery: 1.8±0.5m/s vs. 1.4±0.2m/s, p<0.01. Conclusions Estimation of MW velocities using a novel 3D HFR echocardiography method was feasible in most patients with AMI and all healthy controls. MW velocities were higher in patients compared to healthy controls and infarcted compared to non-infarcted coronary territories. These findings confirm the potential of non-invasive myocardial tissue characterization by MW imaging.Boxplot of MW velocities3D HFR MW visualisation

Three-dimensional deformation imaging to detect myocardial scar

Abstract Introduction Myocardial scar or fibrosis has significant implications in patient management and prognosis. Currently, cardiovascular magnetic resonance (CMR) is the reference technique for detection and quantification of scar though other imaging modalities have been proven to be useful as well. Purpose This study aims to investigate the usefulness of 3D strain echocardiography to identify myocardial scar in patients with ischaemic and non-ischaemic myocardial fibrosis using late gadolinium enhancement (LGE) CMR as a reference. Methods 149 individuals with ischaemic (89), non-ischaemic scar (26) and no scar (34) on LGE CMR underwent 3D transthoracic echocardiography. The 3D data sets were processed with the 4D LV analysis tool by TOMTEC Imaging Systems GmbH, Germany. The longitudinal, circumferential, radial, and principal tangential strain were calculated. Using a 16 LV-segment model the areas of LGE were assessed on CMR images, and a correlation between 3D strain values and LGE was investigated. Results A multivariate binary logistic regression model was built with the conditional backward elimination method using LGE as the dependent variable. The predictors made a significant contribution to the model (Wald test: 49.985, p<0.001). The Cox & Snell R-square was 0.141, and Nagelkerke R-square was 0.232, suggesting that the final model explains 14.1% or 23.2% of LGE variability. By logistic regression analysis, less negative peak principal tangential strain (P-PTS), peak circumferential strain (P-SC), and end-systolic circumferential strain (ES-CS) increased the odds, whereas increased peak radial strain (P-RS) decreased the likelihood of LGE (Table 1). The LGE extent was calculated as the average LGE transmurality of all 16 segments and was used as the dependent variable in linear regression models. The LGE extent was significantly correlated with all strain indices (Table 2). By stepwise linear regression analysis, P-PTS (B=0.029, 95%CI:0.019-0.040, P<0.001) outperformed the remaining strain variables in terms of linear association with LGE extent. Association between strain indices and the presence or absence of myocardial fibrosis in each of the 16 segments was tested by point biserial correlation (Table 3). PTS and CS indices were associated with myocardial fibrosis in 10/16 segments; RS indices were associated with LGE in 9/16 segments, and LS was not related to the presence of LGE in 15/16 segments. Septal (basal-mid-apical) and mid/apical anterior and inferior segmental strain showed more consistent associations with corresponding myocardial fibrosis. Conclusion 3D strain echocardiography is a promising and easily accessible technique, that can be used to identify areas of myocardial scar as it correlates well with LGE in many LV segments. Echocardiography is a bedside and widely available technique, and it could be used in patients with contraindications or no access to CMR or myocardial perfusion scan.Table 3