Effective Regurgitant Orifice Area Research Articles

Prognostic impact of mitral valve geometry in patients with secondary mitral regurgitation: a secondary analysis of the MITRA-FR trial

Abstract Background Mitral valve (MV) transcatheter edge-to-edge repair (TEER) has emerged as a second line therapy on top of guidelines-directed medical treatment (GDMT) in heart failure (HF) patients with severe secondary mitral regurgitation (SMR). Following the disparate results of the COAPT and MITRA-FR pivotal trials, echocardiographic markers of LV remodeling and MR severity have been proposed to select patients most likely to benefit from MV-TEER. The characterization of MV geometry arises as a potential tool to stratify risk of outcomes in SMR patients, who underwent classical surgery or MV-TEER intervention. However, it remains unknown whether MV geometry parameters were associated with prognosis in MITRA-FR patients and whether MV-TEER could modulate their impact on outcomes. Purpose To evaluate the association between MV geometry and outcomes of HF patients with SMR in the MITRA-FR trial, as well as the impact of SMR treatment modality. Methods Thirteen MV geometry parameters were assessed from baseline transthoracic echocardiograms in patients from the MITRA-FR trial. The prognostic impact of MV geometry parameters was studied on top of the baseline clinical variables used in the primary analysis of MITRA-FR (i.e. age, atrial fibrillation [AF], ischemic cardiomyopathy, myocardial infarction, left ventricular ejection fraction [LVEF] and effective regurgitant orifice area [EROA]). The primary endpoint was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. The effect of treatment arms (MV-TEER plus GDMT vs. GDMT alone) on this association was also evaluated. Results Among the 307 patients included in the pivotal trial, 272 were analyzed in the present study (i.e. 135 from the GDMT group and 137 from the GDMT + MV-TEER group). Mean age was 70±10, 74% male. 50% had ischemic cardiomyopathy and 34% AF. LVEF was 33±7% and EROA was 31±11 mm². MV geometry parameters were presented for the whole population and according to the randomization group in the Table. Among these parameters, only MV tenting area remained independently associated with the primary endpoint (Hazard Ratio (HR) = 1.22 per 1 cm², Confidence Interval (CI) = 1.01-1.47; p=0.041) after multivariate analysis (Figure). Tenting height was independently associated with the risk of HFH (HR=1.07 per 1 mm, CI=1.00-1.14, p=0.037), but no MV geometry variable was associated with all-cause death. These findings remained consistent in both treatment arms (p>0.20 for interaction). Conclusion In HF patients with SMR included in the MITRA-FR trial, MV tenting area and MV tenting height were independently associated with the risk of HFH or all-cause mortality and HFH respectively, without any difference according to treatment arms. These data suggest that MV tethering provides an incremental prognostic value beyond classical echocardiographic variables, including EROA, and then should be considered in the risk stratification of patients with HF and SMR.Table of MV geometry parameters featuresMultivariate analysis (Forrest-plots)

Prognostic significance of right ventricle to pulmonary artery coupling acute improvement after mitral transcatheter edge-to-edge repair

Abstract Background Transcatheter Edge-to-Edge Repair (TEER) of mitral valve is a valid treatment option for severe mitral regurgitation. The right ventricle is acutely affected by early hemodynamic changes following the correction of significant mitral regurgitation. Echocardiographic parameters of the right chambers could have a prognostic impact even in a periprocedural setting. In particular, right ventricle to pulmonary artery coupling improvement may be of pivotal importance, as this parameter is a validated marker of right ventricle function. Purpose To evaluate the prognostic impact of early improvement of right ventricle to pulmonary artery coupling assessed by means of the Tricuspid Annular Plane Systolic Excursion/Pulmonary Artery Systolic Pressure (TAPSE/PASP) ratio after TEER. Methods This retrospective single centre study included patients treated with TEER in our hospital from 2015 to 2023. Transthoracic echocardiography was performed before and shortly after device positioning. Acute effects of TEER on echocardiographic parameters were assessed by paired samples t-test. Diagnostic accuracy of the percent variation in the TAPSE/PASP ratio was assessed by means of receiver-operating characteristics analysis. Prognosis was evaluated by Kaplan-Meier analysis. Results The study included 95 patients (age 78 ± 10 years; 63% men; BMI 25 ± 5 kg/m2) with severe or moderate-to-severe mitral regurgitation. Mean baseline Left Ventricle (LV) ejection fraction was 45 ± 16%, LV end-diastolic volume was 157 ± 62 ml and effective regurgitant orifice area was 41 ± 25 mm2. Post-procedural echocardiographic assessment showed early improvement of LV end-diastolic diameter (p < 0.001), LV end-diastolic volume (p = 0.025), LV stroke volume (p < 0.001), LV global longitudinal strain (p < 0.001), right ventricle free wall longitudinal strain (p < 0.001) and PASP (p = 0.002). Percent improvement of TAPSE/PASP ratio showed a sufficient diagnostic accuracy in predicting a composite outcome of hospitalisation for heart failure and all cause mortality at 1 year (area under the curve 0.66, p = 0.047), with an optimal cut-off of 5.5%. An improvement of the TAPSE/PASP ratio over this threshold was associated with a reduction in the composite outcome (hazard ratio 0.38, p = 0.045). Conclusion TEER improves both left and right ventricular dynamics, which can be detected with echocardiography. In particular, an acute improvement of the TAPSE/PASP ratio is associated with an improvement in short-term prognosis. A comprehensive assessment of right ventricular function, including TAPSE/PASP ratio, should be routinely performed before and after TEER.

Efficacy of native T1 mapping for patients with non-ischemic cardiomyopathy and ventricular functional mitral regurgitation undergoing transcatheter edge-to-edge repair

Abstract Background The objectives of this study were to investigate the efficacy of LV myocardial damage assessment by native T1 mapping obtained with cardiac magnetic resonance (CMR) for symptomatic heart failure (HF) patients with non-ischemic cardiomyopathy (NICM) and ventricular functional mitral regurgitation (VFMR) undergoing transcatheter edge-to-edge repair (TEER). Methods We studied 40 symptomatic HF patients with NICM and VFMR undergoing TEER. LV myocardial damage was defined as the native T1 Z-score which was converted from native T1 value obtained with CMR before TEER. The primary endpoint was defined as first re-hospitalization for HF or cardiovascular death over a median follow-up period of 12 months after TEER. Results Multivariable Cox-proportional hazards analysis showed that a native T1 Z-score was the only independent parameter associated with cardiovascular events (hazard ratio: 3.40, 95% confidential interval: 1.51-7.67), and patients with native T1 Z-score < 2.41 experienced significantly fewer cardiovascular events than those with a native T1 Z-score ≥ 2.41 (log-rank P = 0.001). Moreover, such a low native T1 Z-score and more severe VFMR in an effective regurgitant orifice area (EROA) ≥ 0.30 cm2 was associated with fewer cardiovascular events than for a high native T1 Z-score of ≥ 2.41 and less severe VFMR of EROA < 0.30 cm2 (log-rank P = 0.002). Conclusion Assessment of baseline LV myocardial damage by means of native T1 Z-score obtained with CMR without the use of gadolinium-based contrast media is a valuable additional parameter for better management of symptomatic NICM patients with reduced LVEF and VFMR following TEER.

Edge-to-edge repair for tricuspid valve regurgitation: 1-year follow up and clinical implications from the TR- Interventional Study (TRIS)

Abstract Background Tricuspid regurgitation (TR) affects 7% of the population, contributing significantly to heart failure-related hospitalizations. Traditional treatments have several limitations, prompting the exploration of innovative interventions. Purpose The present study aims to investigate the efficacy of tricuspid valve transcatheter edge-to-edge repair (T-TEER) in real-world patients with severe and symptomatic TR deemed at high surgical risk. Primary objectives focus on assessing T-TEER-induced TR reduction and reverse structural remodeling of the RV. Secondary objectives include assessment of functional status, quality of life, and residual regurgitation during the 12-month follow-up period. Methods The TR-Interventional study (TRIS) is a prospective, single-arm study. From January 2021 to December 2023, we enrolled 44 symptomatic patients with at least severe TR referred for TEER. Outcomes included safety and effectiveness along with assessment of clinical status. Results The study cohort had a mean age of 78.3±7 years, with 77.3% women and a mean TRISCORE of 5.1±1.9. Seventeen patients (38.6%) had massive, 7 (15.9%) had torrential, and 20 (45.5%) patients had severe TR. Etiologies included functional (40.9%), degenerative (13.64%), lead-induced (15.9%), and mixed (29.54%) origin. The primary efficacy endpoint, which assesses the successful implantation and performance of the device at the 30-day mark, was attained in 82.9% of patients. The secondary efficacy endpoint, assessing the stability of TR reduction at the 12-month, was achieved in 82,3% of patients. Post-procedural TR reduction of at least 2 degrees was achieved in 84% of patients. Echocardiographic assessments indicate ongoing beneficial remodeling over the one-year follow-up (Figure 1). Effects on RV remodeling also became apparent at the one-year follow-up, including reductions in the RV end-diastolic basal (p<0.01) and medium (p= 0.04) diameters of the TA septal-lateral diameter (p< 0.01). Significant reduction in vena contracta width (9 mm to 3 mm; p=<0.01), regurgitant volume (58 ml to 30 ml; p<0.01), and effective regurgitant orifice area (EROA) (0.6 cm2 to 0.3 cm2; p<0.01), occurred between baseline and one-year follow-up (Figure 2). The NYHA Functional Class and KCCQ scores were improved from 30 days to 1 year (Figure 2). Conclusion TRIS suggests that T-TEER is a durable, effective, and safe therapeutic option for high-risk patients with severe TR. The enduring nature of TR reduction at one year correlates with sustained clinical benefits and reverse structural remodeling of the right ventricle.TR reductionNYHA and functional status

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.

Prognostic stratification of patients with mitral regurgitation using artificial intelligence-enhanced electrocardiogram for left ventricular diastolic function assessment

Abstract Background The determination of left ventricular diastolic dysfunction (LVDD) and filling pressure in patients with significant (>moderate) mitral regurgitation (MR) poses a complex challenge. We recently validated an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm to detect LVDD and estimate LV filling pressures. Methods This retrospective study sought to examine the risk of all-cause mortality across AI-ECG LVDD grades. Patients from the AI-ECG LVDD study test cohort who underwent transthoracic echocardiography confirming significant MR and an ECG within fourteen days of each other at Mayo Clinic between 09/2001 and 06/2022 were included. LVDD status was determined based on the index ECG, and patients were categorized into groups representing normal diastolic function (NDF) or LVDD grades 1 (G1), 2 (G2), or 3 (G3). Results Of 4,019 patients with significant MR (mean age 69.8, 49.0% women), 1,175 (29.2%), 1,881 (46.8%), and 963 (24.0%) were classified by AI-ECG as NDF/G1-LVDD, G2-LVDD, and G3-LVDD, respectively. The median mitral effective regurgitant orifice area was 26 mm² (interquartile range 20-36 mm²). Over a median follow-up of 3.5 years, 1,636 (40.7%) patients died. In multivariable survival analysis adjusted for multiple risk factors, a worse AI-ECG LVDD grade was independently associated with an increased death risk [G2DD: adjusted hazard ratio (aHR) 1.98 (95% confidence interval (95% CI) 1.63-2.40), G3DD: aHR 2.59 (95% CI 2.09-3.20)]. These findings were consistent when accounting for mitral valve intervention and among patients with >moderate MR or after mitral valve intervention. Conclusion In patients with significant MR, the grading of LVDD by AI-ECG is independently associated with all-cause mortality.

Calculation of intraprocedural hemodynamics with computational functional dynamic in mitral valve edge-to-edge repair

Abstract Background Hemodynamic outcomes in patients undergoing transcatheter edge-to-edge-repair of the mitral valve (M-TEER) are difficult to predict. Computational functional dynamic (CFD) is frequently used in biomedical engineering to simulate blood flow patterns under various conditions. The authors developed a standardized workflow for individualized analyses and investigated the hemodynamic of mitral regurgitation volumes and gradients by using CFD. Methods 20 patients from two high volume centers who suffered from severe mitral regurgitation (MR) and underwent full cycle cardiac computed tomography (CT) prior procedure were enrolled. Baseline computed tomography and intraprocedural data were analyzed. Based on the specific valve morphology, individualized CFD-simulations were performed to calculate MR volumes prior to intervention and estimate hemodynamics after M-TEER. Results CFD-analyses of 20 patients (mean age 80±4 years, 60% male) showed excellent correlation between baseline PISA method-based MR volumes (45±23ml) measured in transesophageal echocardiography (TEE) and CFD-based calculation (45±26ml; R=0.917; P<0.001) as well as between TEE-measured mean baseline effective regurgitant orifice area (EROA; 27±16mm²) and CFD-measured EROA (24±18mm²; R=0.869; P<0.001)). After device implantation, correlation between intraprocedural TEE-measured and CFD-estimated correlation for residual MR volumes (R=0.949; P<0.001) and EROA (R=0.841; P<0.001) remained robust. Post-interventional mean diastolic pressure gradient (TEE) was 3.6±2.8mmHg which was in close correlation with the CFD estimated gradient (3.0±1.8mmHg, R=0.905; P<0.001). Conclusions This is the first study to use a CFD-standardized workflow for predicting hemodynamic changes in patients undergoing M-TEER using data from two different centers. In the future, CFD-based analyses might serve as a key-diagnostic tool for predicting residual MR volumes and gradients for M-TEER-procedures.Comparison of TEE and CFD flow patternBland-Altman-Blots

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

The mitral to aortic/pulmonary velocity-time integral ratio is a simple, feasible and accurate discriminator for echocardiographic evaluation of severe isolated mitral regurgitation.

Echocardiographic quantification of mitral regurgitation (MR) remains challenging, requiring dedicated image acquisition, and is limited by potential error from geometric assumptions of annular dimensions. Volume is a product of area and flow and assuming proportional mitral/aortic areas, an increased mitral-inflow volume compared to LV/RV-outflow semi-quantitatively represents greater MR regurgitant volume. Therefore, we investigated the feasibility and diagnostic performance of the mitral-aortic velocity-time integral(VTI) ratio in isolated MR. We also investigated the use of the mitral-pulmonary VTI ratio as an alternative in clinical situations where the LV outflow tract(LVOT) VTI could not be used. We reviewed 166 consecutive patients (33%, n = 54 severe MR by multi-parameter integrated expert opinion). Pulsed wave Doppler VTI at the mitral leaflet tips and the left ventricular outflow and continuous-wave Doppler of the RV outflow tract were measured individually and independently by blinded readers(expert and trainee status) to derive the ratio. Receiver operator characteristic area under the curve(AUC) comparison was calculated and compared with effective regurgitant orifice area(EROA > 40mm), regurgitant volume(RVol > 60mL), vena contracta(VC > 0.7cm), E-velocity > 1.2cm, systolic flow reversal(SFR), left atrial and ventricular dilatation. Increasing ratio was associated with severe MR(AUC 0.94) with optimal threshold defined at 1.3. This provided significant discrimination for severe MR(AUC 0.81) compared to EROA(0.68), VC(0.52), LV dilatation(0.69), LA dilatation(0.70), SFR(0.73), E-velocity(0.68) all p < 0.05, with sensitivity 82% and specificity 94%. The mitral-pulmonary VTI ratio demonstrated similar discrimination(AUC 0.92) with optimal threshold defined at 1.14. Excellent inter-observer reproducibility(intra-class correlation 0.97) was seen between trainee and expert readers. There was no difference in AUC comparison by MR mechanism or patient rhythm. The mitral-aortic and mitral-pulmonary VTI ratios are simple, geometric-free parameters feasibly reproducible from routine echocardiographic datasets and are excellent discriminative tools for severe MR. Readers should consider integration of this parameter in routine reporting.

Comparative analysis of MitraClip/TriClip and PASCAL in transcatheter tricuspid valve repair for tricuspid regurgitation: a systematic review and meta-analysis

BackgroundThe edge-to-edge transcatheter tricuspid valve repair (TTVR) has emerged as a promising technique for the treatment of tricuspid regurgitation (TR). Despite its potential, comparative data on the performance of the novel edge-to-edge devices—MitraClip, PASCAL, and TriClip—remain controversial. In this study, we aim to evaluate the safety and efficacy of these devices in treating TR.MethodsFive databases were systematically searched up to May 2023, with an updated search conducted in May 2024. Only original studies were included in the analysis and were critically evaluated using an adapted version of the Newcastle-Ottawa Scale (NOS) for observational cohort studies and the Cochrane Risk of Bias (ROB) tool for randomized controlled trials.ResultsThe database search yielded 2239 studies, out of which 21 studies were included in the final analysis. These studies encompassed a total of 2178 patients who underwent TTVR using either the MitraClip, TriClip, or PASCAL devices. The risk of bias across these studies ranged from moderate to high. No significant differences were found among the three devices in terms of effective regurgitant orifice area (EROA) and tricuspid regurgitant volume. However, TriClip demonstrated statistically superior efficacy in reducing vena contracta compared to both MitraClip and PASCAL (P < 0.01) [TriClip: (MD = -7.4; 95% CI: -9.24, -5.56), MitraClip: (MD = -4.04; 95% CI: -5.03, -3.05), and PASCAL: (MD = -6.56; 95% CI: -7.76, -5.35)]. The procedural success rates and incidence of single leaflet device attachment (SLDA) were similar across all devices. Furthermore, there were no significant differences in mortality, stroke rates, or major bleeding events among the three devices.ConclusionThe TriClip outperforms the MitraClip and PASCAL in reducing vena contracta width, indicating greater effectiveness for severe tricuspid regurgitation. All devices show similar safety profiles and procedural success rates. Further research is needed to confirm these results.

Exercise testing in patients with tricuspid regurgitation undergoing transcatheter tricuspid valve intervention.

Transcatheter tricuspid valve intervention (TTVI) has shown promising results with persistent reduction of tricuspid regurgitation (TR) and improvements in functional class and quality of life (QOL). To analyze the impact of TTVI on maximal and submaximal exercise capacity (SEC). Constant work-rate exercise-time (CWRET) testing reflects SEC, which is more likely to be relevant for daily life activities and provides more differentiated physiological insight into the nature of exercise intolerance. Thus, 30 patients undergoing TTVI (21 direct annuloplasty and 9 edge-to-edge repair) received cardiopulmonary exercise testing (CPET) and CWRET (at 75% of maximum work rate in the initial CPET) before and 3months after TTVI. Patients' age was 80.5 [74.8-82.3] years and 53.3% were female. TR reduction ≥ 2 grades was achieved in 93.3% (TR grade ≤ moderate in 83.3%). Echocardiography revealed improved right ventricular (RV) characteristics with decreased RV basal diameter (47.0mm [43.0-54.3] vs. 41.5mm [36.8-48.0]; p < 0.001) and decreased inferior caval vein diameter. CWRET testing showed a significantly improved SEC (246.5s [153.8-416.8] vs. 338.5s [238.8-611.8] p = 0.001). Maximum oxygen uptake showed a positive trend without statistically significant differences (9.9ml/min/kg [8.6-12.4] vs. 11.7ml/min/kg [9.7-13.3]; p = 0.31). In contrast to the six-minute-walking distance (6MWD), SEC correlated moderately with effective regurgitation orifice area reduction (r = 0.385; p = 0.036), increased cardiac output (r = 0.378; p = 0.039), and improved QOL (r = 387; p = 0.035). Improvements in exercise capacity after TTVI mainly occur in the submaximal rather than in the maximal exercise range and correlate with hemodynamic effects and QOL. This may have a methodological impact on assessment of exercise capacity in these patients.

Impact of Non-Valvular Atrial Fibrillation on Mitral Valve Anatomic Features: A Study of Three-Dimensional Mitral Valve by Transesophageal Echocardiography and Automatic Analysis Software.

Mitral regurgitation (MR) is frequently observed in non-valvular atrial fibrillation (NVAF) patients and is a significant risk factor for its progression. This study aims to investigate the three-dimensional anatomical characteristics of the mitral valve (MV) in patients with different types of NVAF to elucidate the underlying mechanisms of MR. A retrospective analysis was conducted on 82 paroxysmal atrial fibrillation patients (PAF group) and 66 persistent atrial fibrillation patients (PerAF group) who underwent real-time three-dimensional transesophageal echocardiography (RT 3D-TEE) before initial ablation. Additionally, 30 patients undergoing RT 3D-TEE for the assessment of patent foramen ovale were selected as the control group. Basic echocardiographic variables were measured, left atrioventricular volume and strain parameters were calculated using automated software (Dynamic-HeartModel and AutoStrain). MV anatomic features were analyzed using the 4D-MV Assessment software (TomTec Imaging Systems). The maximum left atrial volume (LAVmax) was highest in the PerAF group, followed by the PAF and control groups, with statistically significant differences (p<0.01). Left atrial reservoir strain (LASr) showed an opposite trend, being the lowest in the PerAF group (p<0.01). The proportion of moderate to severe MR was significantly higher in the PerAF group (27.3%) compared to the PAF group (11.0%) (p<0.01). Compared to controls, the AF groups exhibited mitral annular (MA) dilation, flattening of the MA plane, and increased leaflet area (all p<0.05). Correlation analysis between effective regurgitant orifice area (EROA) and left atrioventricular structure and function parameters, as well as various annular parameters, showed that EROA was significantly correlated with left ventricular end-diastolic volume (LVEDV), LAVmax, LASr, anterior and posterior diameter, annular area, ratio of annular height to commissural diameter (AH/CD ratio), posterior leaflet area, posterior leaflet length, and the C-shaped annulus length (all p<0.05). Significant remodeling of the MV apparatus occurs in NVAF patients, with more pronounced changes in PerAF patients, contributing to a higher incidence of moderate to severe MR. RT 3D-TEE-based MV automated assessment offers significant advantages in accurately diagnosing MV remodeling and supporting the evaluation of MR in NVAF patients.

Novel 3-dimensional effective regurgitation orifice area quantification serves as a reliable tool to identify severe mitral valve regurgitation.

A precise quantification of mitral regurgitation (MR) severity is essential for treatment and outcome of patients with MR. 3D echocardiography facilitates estimation of MR but selection of patients with necessity of invasive treatment remains challenging. We investigate effective regurgitation orifice area (EROA) quantification by 3D compared to 2D echocardiography in patients with MR and highlight the improved discrimination of MR severity. We consecutively enrolled fifty patients with primary or secondary and at least moderate MR undergoing 2D and 3D colour Doppler echocardiography prior to transcatheter edge-to-edge repair (TEER). Improved accuracy of MR grading using 3D vena contracta area (VCA) as an estimate of EROA was compared to 2D proximal isovelocity surface area (PISA) quantification method and a multiparameter reference standard. Quantification of EROA remarkably varies between 2D and 3D echocardiography and the discrimination between moderate and severe MR was significantly (p = 0.001) different using 2D PISA or 3D VCA, respectively. 3D VCA correlated significantly (r = 0.501, p < 0.001) better with the pre-defined MR severity. We detected crucial differences in the correct identification of severe MR between 2D and 3D techniques, thus 2D PISA significantly (p < 0.0001) underestimates EROA due to clinical and morphological parameters. The assessment of 3D VCA resulted in improved diagnostic accuracy.

Revisiting secondary mitral regurgitation threshold severity: insights and lessons from the RESHAPE-HF2 trial.

This article revisits the severity threshold for secondary mitral regurgitation (MR), focusing on insights and lessons from the RESHAPE-HF2 trial. It aims to challenge the traditional effective regurgitant orifice area (EROA) threshold of ≥0.40 cm2 used for intervention, suggesting that earlier intervention may benefit patients with lower EROA. It also explores how transcatheter edge-to-edge repair (TEER) improves outcomes in patients with secondary MR and assesses the impact of left ventricular (LV) remodeling on treatment success. The RESHAPE-HF2 trial evaluated the use of TEER in patients with moderate-to-severe secondary MR, comparing outcomes in those with an EROA ≥0.2 cm2 and no extensive LV remodeling. TEER significantly reduced heart failure hospitalizations and improved quality of life in these patients. This supports the notion that patients with less severe MR, who still show symptoms despite optimal medical therapy, may benefit from earlier intervention. Comparisons with COAPT and MITRA-FR trials underscored the importance of selecting patients based on MR severity relative to LV dilatation. The RESHAPE-HF2 trial highlights the need to reconsider the current EROA threshold for secondary MR intervention. TEER has shown to be beneficial even in patients with lower MR severity, suggesting that earlier intervention could improve outcomes. A more dynamic and integrated approach, considering both MR severity and LV remodeling, is essential for optimizing patient selection and treatment success.

Hospitalization of Symptomatic Patients With HeartFailure and Moderate to Severe Functional Mitral Regurgitation Treated With MitraClip: Insights From RESHAPE-HF2.

For patients with functional mitral regurgitation (FMR) and symptomatic heart failure (HF), randomized trials of mitral transcatheter edge-to-edge repair (M-TEER) have produced conflicting results. This study sought to assess the impact of M-TEER on hospitalization rates, and explore the effects of M-TEER on patients who did or did not have a history of recent HF hospitalizations before undergoing M-TEER. RESHAPE-HF2 (Randomized Investigation of the MitraClip Device in HeartFailure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation) included patients with symptomatic HF and moderate to severe FMR (mean effective regurgitant orifice area 0.25cm2; 14% >0.40cm2, 23%<0.20cm2) and showed that M-TEER reduced recurrent HF hospitalizations with and without the addition of cardiovascular (CV) death and improved quality of life. We now report the results of prespecified analyses on hospitalization rates and for the subgroup of patients (n=333) with a HF hospitalization in the 12months before randomization. At 24months, the time to first event of CV death or HF hospitalization (HR: 0.65; 95%CI: 0.49-0.85; P=0.002), the rate of recurrent CV hospitalizations (rate ratio [RR]: 0.75; 95%CI: 0.57-0.99; P=0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR: 0.74; 95%CI: 0.57-0.95; P=0.017), and of recurrent CV death and CV hospitalizations (RR: 0.76; 95%CI: 0.58-0.99; P=0.040), were all lower in the M-TEER group. The RR of recurrent hospitalizations for any cause was 0.82 (95%CI: 0.63-1.07; P=0.15) for patients in the M-TEER group vs control group patients. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% [95%CI: 13.0%-14.8%] vs 17.4% [95% CI: 16.4%-18.4%] of follow-up time; P< 0.0001, and 1,067 vs 1,776 total days lost; P< 0.0001). Patients randomized to M-TEER also had better NYHA functional class at 30days and at 6, 12, and 24months of follow-up (P< 0.0001). A history of HF hospitalizations before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (Pinteraction=0.03) and of recurrent HF hospitalizations within 24months (Pinteraction=0.06). These results indicate that a broader application of M-TEER in addition to optimal guideline-directed medical therapy should be considered among patients with symptomatic HF and moderate to severe FMR, particularly in those with a history of a recent hospitalization for HF.

Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

Paradox of disproportionate atrial functional mitral regurgitation and survival after transcatheter edge-to-edge repair.

This study aims to assess the applicability of the mitral regurgitation (MR) proportionality concept in patients with atrial functional mitral regurgitation (aFMR) treated with transcatheter edge-to-edge repair (M-TEER). We hypothesized that patients with disproportionate MR (higher MR relative to left ventricular size) would exhibit different outcomes compared to those with proportionate MR, despite undergoing M-TEER. We retrospectively analysed 98 patients with aFMR from the EuroSMR registry who underwent M-TEER between 2008 and 2019. Patients met criteria for aFMR (normal indexed left ventricular end-diastolic volume [LVEDV], preserved left ventricular ejection fraction [LVEF]≥50% without regional wall motion abnormalities, and structurally normal mitral valves). We excluded patients with missing effective regurgitant orifice area (EROA) or LVEDV data. The primary endpoint was 2-year mortality, with an EROA/LVEDV ratio employed to differentiate disproportionate from proportionate MR. Procedural success and baseline characteristics were analysed, and multivariate Cox proportional hazards models were used to identify mortality predictors. The mean patient age was 79±7.3years, with 68.8% female, and 79% had a history of atrial fibrillation. The mean EROA was 0.27±0.14cm2, and LVEDV was 95.6±33.7mL. Disproportionate MR was identified with an EROA/LVEDV ratio >0.339cm2/100mL. While procedural success was similar in both groups, disproportionate MR was associated with a numerically higher estimate of systolic pulmonary artery pressures (sPAP) and rates of NYHA ≥III and TR≥3+. Disproportionate MR had a significant association with increased 2-year mortality (P<0.001). The EROA/LVEDV ratio and tricuspid annular plane systolic excursion (TAPSE) were independent predictors of 2-year mortality (EROA/LVEDV: HR: 1.35, P=0.010; TAPSE: HR: 0.85, P=0.020). This analysis introduces the MR proportionality concept in aFMR patients and its potential prognostic value. Paradoxically, disproportionate MR in aFMR was linked to a 1.35-fold increase in 2-year mortality post-M-TEER, emphasizing the importance of accurate preprocedural FMR characterization. Our findings in patients with disproportionate MR indicate that a high degree of aFMR with high regurgitant volumes may lead to aggravated symptoms, which is a known contributor to increased mortality following M-TEER. These results underline the need for further research into the pathophysiology of aFMR to inform potential preventative and therapeutic strategies, ensuring optimal patient outcomes.

Efficacy of Native T1 Mapping for Patients With Non-Ischemic Cardiomyopathy and Ventricular Functional Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.

We investigated the efficacy of left ventricular (LV) myocardial damage by native T1mapping obtained with cardiac magnetic resonance (CMR) for patients undergoing transcatheter edge-to-edge repair (TEER). We studied 40 symptomatic non-ischemic heart failure (HF) patients and ventricular functional mitral regurgitation (VFMR) undergoing TEER. LV myocardial damage was defined as the native T1Z-score, which was converted from native T1values obtained with CMR. The primary endpoint was defined as HF rehospitalization or cardiovascular death over 12 months after TEER. Multivariable Cox proportional hazards analysis showed that the native T1Z-score was the only independent parameter associated with cardiovascular events (hazard ratio 3.40; 95% confidential interval 1.51-7.67), and that patients with native T1Z-scores <2.41 experienced significantly fewer cardiovascular events than those with native T1Z-scores ≥2.41 (P=0.001). Moreover, the combination of a native T1Z-score <2.41 and more severe VFMR (effective regurgitant orifice area [EROA] ≥0.30 cm2) was associated with fewer cardiovascular events than a native T1Z-score ≥2.41 and less severe VFMR (EROA <0.30 cm2; P=0.002). Assessment of baseline LV myocardial damage based on native T1Z-scores obtained with CMR without gadolinium-based contrast media is a valuable additional parameter for better management of HF patients and VFMR following TEER.

Quantification of Mitral Regurgitation in Mitral Valve Prolapse by Three-Dimensional Vena Contracta Area: Derived Cutoff Values and Comparison With Two-Dimensional Multiparametric Approach

Echocardiographic grading of mitral regurgitation (MR) in mitral valve prolapse (MVP) is challenging. Three-dimensional (3D) vena contracta area (VCA) has been proposed as a valuable method. However, data defining the cutoff values of severity and validation in the subset of patients with MVP are scarce. The aim of this study was to validate the 3D VCA by 3D color-Doppler transesophageal echocardiography (TEE) in patients with MVP and to define the cutoff values of severity grading. The secondary aim was to compare 3D VCA to the effective regurgitant orifice area estimation by proximal isovelocity surface area (EROA-PISA) method. A total of 1,138 patients with at least moderate MR who underwent TEE were included. Three-dimensional VCA was measured, and the cutoff value and area under the curve (AUC) for the prediction of severe MR were estimated by receiver operating characteristic curve using a guideline-suggested multiparametric approach as the reference standard. In a subgroup of patients, 3D regurgitant volume (RV) and 3D fraction were calculated from mitral and left ventricular outflow tract stroke volumes to further validate 3D VCA against a 3D volumetric reference standard. The optimal 3D VCA cutoff value for predicting severe MR was 0.45cm2 (specificity, 0.87; sensitivity, 0.90) with an AUC of 0.95 using a multiparametric approach as reference. Three-dimensional VCA had a good linear correlation with EROA-PISA (r=0.62, P<.05) with larger values compared to EROA-PISA (0.63cm2 vs 0.44cm2, P<.05). A cutoff of 0.50cm2 (AUC of 0.84; sensitivity, 0.78; specificity, 0.78) predicts an EROA-PISA of 0.40cm2. Three-dimensional VCA had a good linear correlation with 3D RV (r=0.56, P<.01), with an AUC of 0.86 to predict a 3D fraction>50%. The present study suggests 0.45cm2 as the best cutoff value of 3D VCA to define severe MR in patients with MVP, showing an optimal agreement with the reference standard multiparametric approach and 3D RV.