Effective Regurgitant Orifice Area Research Articles

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.

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).Methods and Results: 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.

Ecocardiografía transtorácica previa al procedimiento para predecir los resultados de la reparación percutánea de borde a borde en la insuficiencia mitral primaria crónica

Introduction and objectivesLimited data exist on the prognostic usefulness of transthoracic echocardiography preceding MitraClip for chronic primary mitral regurgitation (MR). We evaluated the predictive ability of transthoracic echocardiography in this setting. MethodsA total of 410 patients (median age, 83 years, 60.7% males) were included in the study. The primary outcome was the 1-year composite of all-cause mortality or heart failure hospitalization. Secondary endpoints encompassed individual elements of the primary outcome, the persistence of significant functional impairment or above-moderate MR at 1 year, and above-mild MR at 1-month. ResultsThe only parameter associated with the risk of the primary outcome was a ventricular end systolic diameter index of ≥ 2.1cm/m2, corresponding to the cohort's 4th quartile (HR, 2.44; 95%CI, 1.09-4.68; P=.022). Concurrently, higher left atrial volume index (LAVi) and a mid-diastolic medial-lateral mitral annular diameter (MAD) equal to or above the cohort's median of 32.2 mm were linked to a higher probability of death and heart failure hospitalization, respectively. LAVi of ≥ 60 mL/m2, above-mild mitral annular calcification, and above-moderate tricuspid regurgitation conferred higher odds of functional class III-IV or above-moderate MR persistence. All variables except LAVi and MAD, as well as indexed mid-diastolic medial-lateral MAD of ≥ 20.2 mm/m2 and mitral effective regurgitant orifice area of ≥ 0.40cm2, were associated with greater-than-mild MR at 1 month. ConclusionsPreprocedural increased indexed left heart dimensions, mainly left ventricular end-systolic diameter index, MAD, mitral annular calcification, mitral effective regurgitant orifice area, and tricuspid regurgitation mark a less favorable course post-MitraClip for chronic primary MR.

Initial experience of transcatheter edge-to-edge repair guided by only transesophageal echocardiography in the treatment of tricuspid insufficiency

Objective: To evaluate the feasibility and safety of transcatheter tricuspid valve edge-to-edge repair guided by only transesophageal echocardiography (TEE). Methods: Patients with severe tricuspid regurgitation in Fuwai Yunnan Cardiovascular Hospital who met the inclusion criteria based on clinical and echocardiographic evaluationand underwent transcatheter tricuspid valve edge-to-edge repair between January 2022 and May 2023 were prospectively enrolled. The procedure was performed under general anesthesia with endotracheal intubation and solely guided by TEE. The patients underwent clinical evaluation, electrocardiogram and transthoracic echocardiography one month after the procedure. Results: A total of 22 patients (12 males and 10 females) were included, with an average age of (71.3±6.7) years. All 22 patients successfully underwent the transcatheter tricuspid valve edge-to-edge repair under TEE guidance, with an average of (1.5±0.6) clips implanted. Immediately after procedure, six patients had no or trace regurgitation, 15 patients had mild regurgitation, and one patient had moderate regurgitation. All 22 patients completed 30-day follow-up, with four patients having trace regurgitation, 17 patients having mild regurgitation, and one patient having moderate regurgitation. Echocardiographic measurements revealed that effective regurgitant orifice area, regurgitant volume, vena contracta width, and proximal isovelocity surface area radius significantly decreased after the procedure (all P<0.05). In addition, inferior vena cava width, right atrial volume, tricuspid annular diameter, and right ventricular end-diastolic diameter significantly improved (all P<0.05), but tricuspid annular plane systolic excursion and right ventricular fractional area change did not show significant differences compared with those before the procedure (both P>0.05). Conclusion: It has been preliminarily confirmed that transcatheter tricuspid valve edge-to-edge repair solely guided by TEE is feasible and safe, but requires more large-scale studies for further validation.

Clinical Impact of the Volumetric Quantification of Ventricular Secondary Mitral Regurgitation by Three-Dimensional Echocardiography

The assessment of ventricular secondary mitral regurgitation (v-SMR) severity through effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) calculations using the proximal isovelocity surface area (PISA) method and the two-dimensional echocardiography volumetric method (2DEVM) is prone to underestimation. Accordingly, we sought to investigate the accuracy of the three-dimensional echocardiography volumetric method (3DEVM) and its association with outcomes in v-SMR patients. We included 229 patients (70±13years, 74% men) with v-SMR. We compared EROA and RegVol calculated by the 3DEVM, 2DEVM, and PISA methods. The end point was a composite of heart failure hospitalization and death for any cause. After a mean follow-up of 20±11months, 98 patients (43%) reached the end point. Regurgitant volume and EROA calculated by 3DEVM were larger than those calculated by 2DEVM and PISA. Using receiver operating characteristic curve analysis, both EROA (area under the curve, 0.75; 95% CI, 0.68-0.81; P=.008) and RegVol (AUC, 0.75; 95% CI, 0.68-0.82; P=.02) measured by 3DEVM showed the highest association with the outcome at 2years compared to PISA and 2DEVM (P<.05 for all). Kaplan-Meier analysis demonstrated a significantly higher rate of events in patients with EROA ≥ 0.3cm2 (cumulative survival at 2years: 28%±7% vs 32%±10% vs 30%±11%) and RegVol ≥ 45mL (cumulative survival at 2years: 21%±7% vs 24%±13% vs 22%±10%) by 3DEVM compared to those by PISA and 2DEVM, respectively. In Cox multivariable analysis, 3DEVM EROA remained independently associated with the end point (hazard ratio, 1.02, 95% CI, 1.00-1.05; P=.02). The model including EROA by 3DEVM provided significant incremental value to predict the combined end point compared to those using 2DEVM (net reclassification index=0.51, P=.003; integrated discrimination index=0.04, P=.014) and PISA (net reclassification index=0.80, P<.001; integrated discrimination index=0.06, P<.001). Effective regurgitant orifice area and RegVol calculated by 3DEVM were independently associated with the end point, improving the risk stratification of patients with v-SMR compared to the 2DEVM and PISA methods.

A Comparative Study of 1-Year Postprocedural Outcomes in Transcatheter Mitral Valve Repair in Advanced Primary Mitral Regurgitation: PASCAL vs. MitraClip.

Both the MitraClip and PASCAL systems offer transcatheter edge-to-edge repair (TEER) solutions for mitral regurgitation. Evidence indicates a lower technical success rate for TEER in complex degenerative mitral regurgitation (DMR) cases. We conducted a retrospective analysis of patients who underwent transcatheter edge-to-edge therapy for primary mitral regurgitation with advanced anatomy, defined as mitral regurgitation effective regurgitant orifice area (MR-EROA) ≥0.40 cm2 or large flail gap (≥5 mm) or width (≥7 mm) or Barlow's disease, that completed follow-up after 1 year. Our criteria were met by 27 patients treated with PASCAL and 18 with MitraClip. All patients exhibited a significant, equivalent short-term reduction in MR-EROA, mitral regurgitation vena contracta diameter (MR-VCD), regurgitant volume, and clinical status. At 1 year follow-up, reductions in MR-VCD, regurgitant volume, and MR-EROA remained significant for both groups without significant differences between groups. MR-Grade ≤ 1+ was achieved in 18 (66.7%) and 10 (55.6%) patients, respectively. At follow-up, no difference in hospitalization for cardiac decompensation was observed. Overall death was similar in both groups. Our study suggests that both the PASCAL and MitraClip systems significantly reduce mitral regurgitation even in advanced degenerative diseases. Within our limited data, we found no evidence of inferior performance of the PASCAL system.

In vitro and clinical validation of different correction algorithms for the two-dimensional proximal isovelocity surface area method in a low-velocity flow field for quantifying tricuspid regurgitation.

The 2-dimensional proximal isovelocity surface area (2D PISA) method underestimates tricuspid regurgitation (TR) severity. Previously proposed correction algorithms should be further scrutinized. Two correction algorithms were tested. One approach involves dividing the 2D PISA effective regurgitant orifice area by a constant of 0.7 (EROA0.7). Another approach involves multiplying the unadjusted EROA by Vorifice/(Vorifice - Valiasing), where Vorifice denotes the TR jet velocity, and Valiasing represents the color aliasing velocity (EROAVo-Va). In vitro validation was performed on a commercially available multifunctional valve tester with different size orifices and peak pressure gradients. A true EROA was derived through the regurgitant volume (RVol) calculated from the tester. For clinical validation, RVol was calculated as the difference between the overall stroke volume and the forward stroke volume of the right ventricle. Volumetric EROA was derived by dividing the RVol by the TR velocity-time integral (VTI). The vena contracta area (VCA) was obtained through direct planimetry with 3D echocardiography. The mean of volumetric EROA and VCA served as the reference in clinical validation. Excellent correlation between the calculated EROAs and the true EROA was observed in vitro (r=0.98, r=0.97, and r=0.98 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively; all P values <0.0001). EROAVo-Va underestimated the true EROA and averaged 33% (P=0.3163), while EROA0.7 overestimated the true EROA and averaged 8% (P=0.0032). Clinically, these methods consistently exhibited a notable underestimation that varied with the reference EROA. This systematic underestimation was mitigated by both algorithms when either the VCA (biases of 19.6, 15.1, and 11.8 mm2 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively) or the volumetric EROA (biases of 10.1, 5.6, and 2.3 mm2 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively) served as the reference. Their ability to distinguish severe TR was similar, with area under the curve values of 0.905, 0.903, and 0.893 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively. No statistically significant differences were observed for diagnostic accuracy (all P values >0.05). Using a correction factor of 0.7 in quantifying TR provides similar accuracy when compared to other techniques. This represents a valuable clinical tool for quickly correcting the underestimation of the 2D PISA method in TR. This simple method may increase the frequency of applying the correction and earlier recognition of patients with severe TR.

Challenges and pitfalls in classification of disproportionate mitral regurgitation.

The concept of disproportionate mitral regurgitation (dispropMR) has been introduced to identify patients with functional mitral regurgitation (MR) who benefit from percutaneous treatment. We aimed to examine echocardiographic characteristics behind this entity. We retrospectively included 172 consecutive patients with reduced left ventricular ejection fraction (LVEF), and more than mild MR referred to clinically indicated echocardiography. According to the proportionality ratio (effective regurgitant orifice area (EROA)/left ventricular end-diastolic volume (LVEDV)) patients were divided into dispropMR and proportionate MR (propMR) group. Potential factors which might affect proportionality definition were analyzed. 55 patients (32%) had dispropMR. Discrepant grading of MR severity was observed when using regurgitant volume (RegVol) by proximal isovelocity surface area (PISA) method or volumetric method, with significant discordance only in dispropMR (p < 0.001). Patients with dispropMR had more frequently left ventricular foreshortened images for LVEDV calculation than patients with propMR (p = 0.003), resulting in smaller LVEDV in dispropMR group. DispropMR group had more substantial dynamic variation of regurgitant flow compared to propMR. Accordingly, EROA was consistently overestimated by standard single-point PISA method compared to serial PISA method. This was more pronounced in dispropMR (bias:10.5 ± 28.3 mm2) compared to propMR group (bias:6.4 ± 12.8 mm2). DispropMR may be found in roughly one third of clinically indicated echocardiographic studies in patients with reduced LVEF and more than mild MR. EROA overestimation due to dynamic variation of regurgitant flow and LVEDV underestimation due to LV foreshortening were more frequently found in dispropMR. Our results indicate that methodological limitations of echocardiographic MR grading could not be neglected in classifying the proportionality of MR.

Preprocedural transthoracic echocardiography for predicting outcomes of transcatheter edge-to-edge repair for chronic primary mitral regurgitation

Introduction and objectivesLimited data exist on the prognostic usefulness of transthoracic echocardiography preceding MitraClip for chronic primary mitral regurgitation (MR). We evaluated the predictive ability of transthoracic echocardiography in this setting. MethodsA total of 410 patients (median age, 83 years, 60.7% males) were included in the study. The primary outcome was the 1-year composite of all-cause mortality or heart failure hospitalization. Secondary endpoints encompassed individual elements of the primary outcome, the persistence of significant functional impairment or above-moderate MR at 1 year, and above-mild MR at 1-month. ResultsThe only parameter associated with the risk of the primary outcome was a ventricular end systolic diameter index of ≥2.1 cm/m2, corresponding to the cohort's 4th quartile (HR, 2.44; 95%CI, 1.09-4.68; P=.022). Concurrently, higher left atrial volume index (LAVi) and a mid-diastolic medial-lateral mitral annular diameter (MAD) equal to or above the cohort's median of 32.2mm were linked to a higher probability of death and heart failure hospitalization, respectively. LAVi of ≥ 60mL/m2, above-mild mitral annular calcification, and above-moderate tricuspid regurgitation conferred higher odds of functional class III-IV or above-moderate MR persistence. All variables except LAVi and MAD, as well as indexed mid-diastolic medial-lateral MAD of ≥ 20.2mm/m2 and mitral effective regurgitant orifice area of ≥ 0.40 cm2, were associated with greater-than-mild MR at 1 month. ConclusionsPreprocedural increased indexed left heart dimensions, mainly left ventricular end-systolic diameter index, MAD, mitral annular calcification, mitral effective regurgitant orifice area, and tricuspid regurgitation mark a less favorable course post-MitraClip for chronic primary MR.

Comparison of effective regurgitant orifice area by the PISA method and tricuspid coaptation gap measurement to identify very severe tricuspid regurgitation and stratify mortality risk

Abstract Background Various definitions of very severe (VS) tricuspid regurgitation (TR) have been proposed based on the effective regurgitant orifice area (EROA) or tricuspid coaptation gap (TCG). Because of the inherent limitations associated with the EROA, we hypothesized that the TCG would be more suitable for defining VSTR and predicting outcomes. Purpose To compare EROA and TCG for outcome prediction in patients with severe TR. Methods In this French multicentre retrospective study, we included 606 patients with ≥ moderate-to-severe isolated TR (without structural valve disease or an overt cardiac cause) according to the recommendations of the European Association of Cardiovascular Imaging. Patients were further stratified into VSTR according to the EROA (≥60 mm²) and then according to the TCG (≥10 mm). The primary endpoint was all-cause mortality and the secondary endpoint was cardiovascular mortality. Results The relationship between the EROA and TCG was poor (R²=0.21), especially when the size of the defect was large. Four-year survival was comparable between patients with an EROA &amp;lt;60 mm² vs. ≥ 60 mm² (67±3% vs. 64±4%, p=0.64), even after adjustment, for all-cause (p=0.72) and cardiovascular mortality (p=0.18). A TCG ≥10 mm was associated with lower four-year survival than a TCG &amp;lt;10 mm (53±7% vs. 69±3%, p&amp;lt;0.001). After adjustment for covariates, including age, comorbidity, right heart failure, dose of diuretics, and right ventricular dysfunction, a TCG ≥10 mm remained independently associated with higher all-cause mortality (adjusted HR[95%CI]=1.46[1.15-2.18], p=0.015) and cardiovascular mortality (adjusted HR[95%CI]=1.95[1.22-3.14], p &amp;lt;0.001), whereas an EROA ≥60 mm² was not associated with all-cause or cardiovascular mortality (adjusted HR[95%CI]:1.07[0.75-1.51], p=0.720, and adjusted HR[95%CI]:1.35[0.87-2.09], p=0.176, respectively). Conclusion The correlation between the TCG and EROA is weak and decreases with increasing defect size. A TCG ≥10mm is associated with increased all-cause and cardiovascular mortality and should be used to define VSTR in isolated TR.Correlation between EROA and TCGEvent free survival curves

Relative size of the effective regurgitant orifice to right ventricular cavity contributes significantly to the underestimation of 2D PISA method in tricuspid regurgitation quantitation

Abstract Background 2D proximal isovelocity surface area (PISA) method underestimates tricuspid regurgitation (TR) severity largely due to the distortion of proximal flow geometry under low jet velocity. Previous studies demonstrated that the confining wall geometry also strained the streamline distribution in the proximal flow field. This could add to the variability when applying 2D PISA in TR as TR presents with wider range of effective regurgitant orifice area (EROA). Purpose We aim to examine (1) the impact of ventricular wall constraint to proximal flow region on TR quantitation and (2) its relative contribution to the underestimation of 2D PISA compared with the distortion of proximal flow field under low jet velocity. Methods 150 pts with more than mild TR underwent comprehensive echocardiographic session. The standard 2D PISA EROA (EROASD)was derived as per guideline with angle correction applied for tethering leaflets. The underetimation caused by low jet velocity was corrected by multiplying the standard EROA (EROASD) with VOrifice/(VOrifice-VNyquist), where the VOrifice stands for the peak regurgitant velocity and the VNyquist represents the color Doppler aliasing velocity (EROAVo-VN). The volumetric EROA and vena contracta area serves as two independent reference methods. The ventricular wall constraint was quantified as the ratio of reference EROA to right ventricular end-diastolic volume (RVEDV). Results A consistent significant underestimation by standard 2D PISA methods, either corrected for low jet velocity or not, was observed as a function of the EROA (Figure 1). In Bland-Altman analysis, correction for low jet velocity lessened the systematic underestimation but still leaves minor while could-be-important error (VCA, bias = 19.6 and 15.1 mm2; volumetric EROA, bias = 10.1 and 5.6 mm2 for EROASD and EROAVo-VN respectively). The accuracy of both methods to differentiate severe TR was similar but the cut-off values were lower compared with guideline recommendation (AUC = 0.905 and 0.903, cut-off = 0.26 and 0.29 cm2 for EROASD and EROAVo-VN respectively). In multi-linear regression model (Table 1), the difference between standard 2D PISA EROA and reference EROA (mean of volumetric EROA and vena contracta area) was significantly related to etiology, the jet velocity-related correction coefficient, and the reference EROA/RVEDV ratio. The ventricular wall constraint contributes to the underestimation of 2D PISA to a greater extent than the low jet velocity (beta = -0.269 and 0.592 for VOrifice/(VOrifice-VNyquist) and reference EROA/RVEDV respectively). Conclusion Correction for low jet velocity lessens the extent of underestimation of TR severity by 2D PISA method but still leaves important measurement error. The confining wall geometry to proximal flow region contributes significantly to the understimation but is not accounted for in current recommendation. This could be especially important in massive and torrential TR.

Efficacy and evolution of edge-to-edge transcatheter valve repair procedures

Abstract Background Edge-to-edge transcatheter mitral valve repair (M-TEER) has shown safety and efficacy in reducing secondary mitral regurgitation (MR) (1,2) and led to the development of similar devices for transcatheter valve repair (T-TEER) for tricuspid regurgitation (TR) (Fig. 1A). However, T-TEER implementation is challenging due to complex valve anatomy and periprocedural imaging. We sought to understand to which extent procedural success of M-TEER changed over time and possibly impacted T-TEER results. Methods We retrospectively analyzed intraprocedural reduction of secondary MR and TR after release of a valve specific device, between 2018, when M-TEER was implemented in our center, through 2020, when T-TEER procedures started, and up to the end of 2022. We compared results between the 55 T-TEER procedures performed (age 81.8±4.7, 55% females) and 3 M-TEER cohorts: the very first 55 M-TEER, the last 55 M-TEER before T-TEER, and the very last 55 M-TEER (overall mean-age 78.4±8.2, 49% females) (Fig. 1B). Severe MR III/IV was defined by an effective regurgitation orifice area (EROA) of 20-39mm², and IV/IV by EROA ≥40mm², while TR was evaluated using the I/V to V/V classification. Considering that a 5-grade reduction of TR is either not possible or not desirable, the extension of regurgitation reduction for both valves was set on a scale from 1- to 4-grade. Also, optimal results were defined as residual MR 0+ (none or trace) or TR I+ (mild or mild to moderate), while acceptable results were considered MR I+ and TR II+ (moderate or moderate to severe). Results In all groups, regurgitation was successfully and significantly reduced within-group (Fig. 1C). MR reduction to optimal or acceptable levels increased over time from 60% at the start of the M-TEER program to 78% after 12-18 months (p=0.039), and 84% (p=0.005) after approximately 3 years. Accordingly, the extent of regurgitation reduction significantly improved between the first 2 M-TEER cohorts (p=0.016), as well as the first and the last 55 M-TEER (p=0.045), with no significant change from the second to the third population (p=0.267) (Fig. 2). Two years after the first M-TEER, T-TEER with valve specific devices was implemented and achieved 84% optimal or acceptable residual TR, better than initial M-TEER (p=0.005) and similar to the second (p=0.466) and third M-TEER cohorts (p=1.000). In terms of extent of regurgitation reduction, T-TEER also performed similar to the very first (p=0.645) and the very last M-TEER procedures (p=0.076), despite higher mean-EROA (78.5±32.2mm² vs 44.8±16.1mm² in all MR patients, p&amp;lt;0.001), more complex anatomy, more challenging imaging, and sicker patients (mean-EuroSCORE II 8.8±6.6% vs 6.4±5.3% in all MR patients, p&amp;lt;0.001). Conclusions In our center, gain in knowledge and experience, coupled with technological advances, have significantly impacted procedural M-TEER success over time and allowed similar successful implementation of a T-TEER program.Figure 1Figure 2

NYHA class IV in patients with degenerative mitral regurgitation undergoing transcatheter edge-to-edge repair: Results of the worldwide, multicenter PRIME-MR registry

Abstract Background Patients with degenerative mitral regurgitation (DMR) presenting with resting dyspnoea (New York Heart Association [NYHA] class IV), particularly in cases of acute onset or rapid deterioration, constitute a high-risk cohort with significant implications for preprocedural planning. This study aims to assess whether preprocedural NYHA class IV is associated with adverse events and outcomes in DMR patients undergoing Transcatheter mitral edge-to-edge repair (TEER), by analyzing data from the PRIME-MR registry. Methods PRIME-MR, a retrospective, investigator-initiated, multicenter registry, comprises patients who underwent TEER for relevant DMR in 24 high-volumes centres between 2008 and 2022. The primary objective was to evaluate the outcomes of patients with resting dyspnoea (defined as NYHA class IV at baseline) and compare these to patients presenting with NYHA class II or III. Results In this analysis, 1,941 consecutive patients (median age: 81 years [IQR 76; 85]; 46.8% female; mean STS Mortality Score [mitral repair]: 5.0% ± 3.9) with available follow-up data were included (median follow-up time 2.56 years [95%-confidence interval 2.39; 2.47]). Of these patients, 323 (16.6%) presented with NYHA class IV at baseline. There were no differences at baseline in terms of median left ventricular ejection fraction (NYHA IV: 58% [IQR 50; 64] vs. NYHA II/III: 60% [IQR 50; 65]; p=0.30) or right ventricular function, measured by TAPSE (NYHA IV: 19mm [IQR 15; 22] vs. NYHA II/III: 19mm [IQR 16; 23]; p=0.088). DMR severity was comparable between the groups (effective regurgitation orifice area [EROA]: NYHA IV 0.5cm² [IQR 0.4; 0.7] vs. NYHA II/III: 0.4cm² [IQR 0.3; 0.6]; p=0.052). The main pathology differed between both groups, with higher proportions of flails in patients with NYHA IV (57.3% [n=142] vs. NYHA II/III: 48.4% [n=674]; p=0.013). NYHA class IV patients had higher median levels of baseline NT-proBNP (NYHA IV: 3182ng/L [1411; 7966] vs. NYHA II/III: 1875ng/L [IQR 803; 3968]; p&amp;lt;0.001). Functional success rates according to M-VARC criteria (residual mitral regurgitation [rMR] ≤2+, EROA ≤0.15cm², transmitral pressure gradient ≤5 mmHg) were comparable (NYHA IV: 71.4% [n=200] vs. NYHA II/III: 73.5% [n=1060]; p=0.52). Postprocedural efficacy was high in both groups (rMR ≤2+ at discharge in NYHA IV: 87.4% [n=243] vs. NYHA II/III: 90.4% [n=1,344]; p=0.59; Figure 1). However, Kaplan-Meier analysis for all-cause mortality or rehospitalization after two years revealed worse outcomes of patients with NYHA IV (log-rank p=0.002; Figure 2). Conclusion This analysis of the PRIME-MR registry revealed that, despite similar baseline characteristics and high procedural efficacy in both groups, the presence of NYHA class IV at baseline was associated with inferior clinical outcomes in DMR patients undergoing TEER. As such, it represents an important indicator of increased risk of mortality and rehospitalization and may require closer patient follow-up.MR at baseline and dischargeKaplan Meier analysis

Dapagliflozin effect on functional mitral regurgitation and myocardial remodeling (DEFORM trial)

Abstract Background Functional mitral regurgitation (FMR) has already been demonstrated to lead to various adverse outcomes. However, the therapeutic effect of current guideline-directed medical therapy (GDMT) in FMR still remained limited. The purpose of this study was to assess the efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin in reducing the extent of mitral regurgitation and myocardial remodeling in FMR patients. Methods In this prospective, randomized, parallel controlled trial, we randomly assigned 104 patients with moderate or severe FMR in a 1:1 ratio to receive either dapagliflozin 10mg once daily or not in addition to GDMT for FMR and follow-up for 12 weeks. The primary outcome was the change in effective regurgitant orifice area (EROA) of mitral regurgitation. Secondary outcomes included changes in regurgitant volume (RV), left atrial dimension (LAD), left ventricular end-systolic dimension (LVESd), left ventricular end-diastolic dimension (LVEDd), left ventricular ejection fraction (LVEF) and E/e’ ratio. Furthermore, we additionally compared the occurrence rate of hospitalization for heart failure or cardiac death between groups. Results Dapagliflozin was associated with a significant reduction in EROA of FMR (-0.074±0.099 vs -0.030±0.058 cm2for dapagliflozin vs. control, P=0.008). Dapagliflozin was also associated with significant reduction of RV (-9.08±15.27 vs. -2.98±9.28 ml for dapagliflozin vs. control, P=0.017), LAD (-2.45±4.44 vs. -0.36±3.08 mm for dapagliflozin vs. control, P=0.007) and E/e’ ratio (-5.88±7.41 vs -1.98±7.63 for dapagliflozin vs. control, P=0.011), and improvement in LVEF (6.57±10.10 vs. 1.92±9.57 for dapagliflozin vs. control, P=0.017). There were no significant differences in the changes of LVESd (P=0.662) and LVEDd (P=0.677) between groups. Hospitalization for heart failure occurred in 6 patients of dapagliflozin group (11.5%) and 10 patients of control group (19.2%) (log-rank test, P=0.257), and 1 patient in dapagliflozin group (1.9%) and 2 patients in control group (3.8%) had cardiac death during the 12-week follow-up (log-rank test, P=0.552). Conclusion Dapagliflozin could further reduce the extent of mitral regurgitation and improve myocardial remodeling in FMR patients based on the current GDMT. Our findings suggest that SGLT-2 inhibitors might be considered for GDMT of patients with moderate or severe FMR.

Rate of progression of tricuspid regurgitation and clinical implications

Abstract Background Tricuspid regurgitation (TR) is a prevalent valvular disease. Recent studies demonstrated that significant TR is associated with an increased mortality. However, information regarding the progression rate of TR is lacking, crucial for the correct clinical evaluation of such patients. Due to this fact, current guidelines fail to propose a scheduled follow-up programme in patients with significant TR; contrary to patients with left-sided valvular disease. The aim of this study is to examine the rates of TR progression and its clinical implications. Objectives To analyse the rate of progression of TR during follow-up and evaluate the impact of TR progression in hospitalizations due to heart failure (HF) or cardiovascular (CV) death. Methods 1843 patients with at least moderate TR were prospectively followed up with consecutive echocardiographic studies and/or clinical evaluation. Clinical and echocardiographic features were recorded to assess their impact in TR progression. TR progression was defined as at least worsening of one grade according to Hahn and Zamorano classification based on Vena contracta width and effective regurgitant orifice area. The cumulative event rates were estimated with the Kaplan-Meyer method and compared by means of the log-rank test. Results Median follow-up time was 3.7 (IQR: 1.2 to 3.8) years. During the follow-up period, death occurred in 525 patients (28.5%); due to cardiovascular causes in 174 (9.4%) of them. Figure 1 shows the incidence of TR progression from moderate to at least severe TR during follow-up period. Moderate TR had 4.9%, 10.1% and 24.8% 1-year, 2-year and 3-year risk of progression to at least severe TR, respectively. The combined endpoint of cardiovascular mortality and hospitalization for heart failure was higher among progressors (23.5% vs. 37.7%; log rank P &amp;lt; 0.001, Figure 2). Conclusions Progression of TR is associated with an increased risk of hospitalizations and cardiovascular mortality. According to the rate of progression in our study, we support serial echocardiographic testing for these patients similar to that proposed by current guidelines for left-sided heart disease. However, we still need evidence of the impact of serial testing in TR.Incidence of TR progression from moderatKaplan Meier survival curves free from h

Preoperative predictors of recurrent tricuspid regurgitation after annuloplasty: insights into the role of 3D echocardiography

Abstract Introduction There is a growing concern regarding the recurrence of tricuspid regurgitation (TR) after tricuspid annuloplasty (TA) in patients with functional tricuspid regurgitation (FTR). While TA is an effective treatment option, understanding the echocardiographic factors contributing to recurrent TR can help in developing more effective preventive measures to reduce the rate of recurrent TR after TA. Aim The aim is to investigate the relationship between tricuspid valve (TV) and right ventricular geometry and function parameters with recurrent TR after TA. Methods This study was designed as a prospective observational cohort study to investigate factors contributing to recurrent TR following surgical TV repair in patients with moderate or severe functional TR caused by left heart valvular disease, with severe mitral regurgitation as the dominant pathology. Patients with ischemic heart disease were excluded from the analysis. The study included 65 patients who underwent preoperative 2D and 3D echocardiographic assessments, which included the quantification of right ventricular (RV) and right atrial (RA) geometry, functional and TV parameters. The severity of TR was measured according to the recent ESC guidelines, and patients were divided into two groups based on the outcomes of TA: effective TA (43 patients) and recurrent TR group (22 patients). Effective TA was defined as mild TR one year after surgery, while recurrent TR group was defined as moderate or severe TR. Statistical analysis was conducted using SPSS statistical software. Results Of the patients, 54% were male, and the mean age was 68±9 years. The distribution of echocardiography parameters among the study groups are shown in Table 1. Analysis revealed that gender, left ventricular and atrial geometrical and functional parameters, or preoperative effective regurgitant TV orifice area did not differ between the groups (recurrent TR vs. effective TA: 33 [28] mm2 vs. 29 [18] mm2, p=0.113 respectively). However, recurrent TR was associated with dilated RV and RA parameters and an increased septal-lateral diameter of tricuspid annulus. RV functional parameters did not show significant associations. Of all preoperative parameters, RV middle (sensitivity 82%, specificity 63%; AUC 0.731) and basal (sensitivity 73%, specificity 65%; AUC 0.725) diameters, tricuspid annulus sphericity index (sensitivity 59%, specificity 70%; AUC 0.718), septal-lateral systolic (sensitivity 59%, specificity 76%; AUC 0.686) diameter, have the highest predictive value for recurrent TR. Conclusion Recurrent moderate or severe functional TR after TA is associated with preoperative tricuspid annulus size, RA and RV geometry, but not with changes of RV function. This information can guide surgical decision-making. To conclude with, improving our understanding of the factors contributing to recurrent TR after TA can improve patient outcomes and reduce the need for reoperations.

Disproportionate MR and 5-year mortality following acute heart failure hospitalisation

Abstract Background The clinical implications of disproportionate mitral regurgitation (DispMR) is contentious and uncertainty remains if this cohort of patients benefit from intervention. Its prognostic significance in acute heart failure remains incompletely investigated. Purpose To examine whether DispMR, defined by the ratio of the effective regurgitant orifice area (ERO)/LVEDV &amp;gt;0.14mm2/ml, is an independent predictor of long-term mortality following hospitalisation for AHF. Methods 418 consecutive AHF patients were recruited and followed up for the primary outcome of all-cause, 5-year mortality. A key secondary outcome was cardiovascular (CV) death. Patients were recruited if they displayed signs and symptoms of AHF, had point-of-care brain-natriuretic peptide &amp;gt;100pg/ml and had evidence of AHF on comprehensive bedside transthoracic echocardiography. 30 variables encompassing age, gender, BMI, a history of COPD, CKD, hypertension, diabetes, previous CVA, CAD, AF on admission ECG, admission systolic BP, NYHA classification, heart rate, Na, BNP, urea, anaemia, LA size, RA size, TR severity, lateral E/e’ &amp;gt;14, RV diastolic area, TAPSE, SPAP, LVEF phenotype, a loop diuretic, MRA, beta-blocker, ARB/ACE-I, CCB or statin prescribed on discharge were included. Multivariate Cox-proportional hazard models were constructed to test for an independent prognostic role of DispMR. Missing outcome data was right-censored. Results 313/418 (74.8%) displayed secondary MR and had quantifiable ERO and LVEDV (median age 81, 53.4% male) and were included in analysis. 217/313 (66.5%) displayed DispMR. Kaplan-Meier curve analysis revealed worse all-cause mortality in DispMR vs. proportionate MR (HR 1.72 95% CI 1.31-2.27 [p&amp;lt;0.001]). On multivariable analysis DispMR was independently associated with all-cause mortality (HR 1.77 (95% CI 1.26-2.51 [p=0.0012]). 284/313 (90.7%) had CV mortality data available. DispMR was associated with increased risk of 5-year, unadjusted, CV mortality compared to proportionate MR (HR 1.72 95% CI 1.31-2.27 [p&amp;lt;0.001]). These effects were present across all ejection fraction phenotypes. Conclusions Among patients with quantifiable MR in AHF, the presence of DispMR was independently associated with long-term outcome. These results suggest assessment of MR within the context of LV volumes can identify patients at increased risk and should have implications for future guidelines.

Impact of Transcatheter Edge-to-Edge Mitral Valve Repair on Atrial Functional Mitral Regurgitation from the GIOTTO Registry

Atrial functional mitral regurgitation (aFMR) has a peculiar pathophysiology that may have distinctive outcomes. We investigated the impact of transcatheter edge-to-edge repair in aFMR compared with other FMR etiologies. The GIOTTO (GIse registry Of Transcatheter treatment of MR) is a multicenter, prospective study enrolling patients with symptomatic MR treated with MitraClip up to 2020. We categorized patients with FMR as aFMR, ischemic FMR (iFMR), and nonischemic ventricular FMR (niFMR). The clinical end points were defined according to the Mitral Valve Academic Research Consortium. Of 1,153 patients, 6% had aFMR, 47% iFMR, and 47% niFMR. Patients with aFMR were older, mostly women, and had a higher atrial fibrillation rate. They had better left ventricular ejection fraction and smaller left ventricular volumes, with no difference in mitral effective regurgitant orifice area. The acute device and procedural success rates were similar among the groups. At the longest available follow-up (median 478days, interquartile range 91 to 741 days), the rate of MR ≥2+ was similar among the groups. Patients with aFMR had a lower rate of cardiovascular death and heart failure than patients with iFMR (hazard ratio [HR] 0.43, p = 0.02) and niFMR (HR 0.45, p = 0.03). The aFMR etiology remained independently associated with the composite outcome, together with postprocedural MR ≤1+ (HR 0.63, p <0.01) and peripheral arteriopathy (HR 1.82, p = 0.003). The results of this GIOTTO subanalysis suggested that aFMR is less prevalent and associated with better outcomes compared with other causes of FMR treated by transcatheter edge-to-edge repair. Postprocedural MR >1+, peripheral vasculopathy, non-aFMR were independent predictors of worse outcomes.