Effective Regurgitant Orifice 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.

Reappraisal of the Concept and Implications of Pulmonary Hypertension in Degenerative Mitral Regurgitation

BackgroundEuropean and U.S. clinical guidelines diverge regarding pulmonary hypertension (PHTN) in degenerative mitral regurgitation (DMR). Gaps in knowledge underpinning these divergences affect risk assessment and management recommendations attached to systolic pulmonary pressure (SPAP) in DMR. ObjectivesThis study sought to define PHTN links to DMR severity, prognostic thresholds, and independent outcome impact in a large quantitative DMR registry. MethodsThis study gathered a large multicentric registry of consecutive patients with isolated moderate-to-severe DMR, with DMR and SPAP quantified prospectively at diagnosis. ResultsIn 3,712 patients (67 ± 15 years, 36% women) with ≥ moderate-to-severe DMR, effective regurgitant orifice (ERO) was 0.42 ± 0.19 cm2, regurgitant volume 66 ± 327 mL/beat and SPAP 41 ± 16 mm Hg. Spline-curve analysis showed excess mortality under medical management emerging around SPAP 35 mm Hg and doubling around SPAP 50 mm Hg. Accordingly, severe pulmonary hypertension (sPHTN) (SPAP ≥50 mm Hg) was detected in 916 patients, moderate pulmonary hypertension (mPHTN) (SPAP 35-49 mm Hg) in 1,128, and no-PHTN (SPAP <35 mm Hg) in 1,668. Whereas SPAP was strongly associated with DMR-ERO, nevertheless excess mortality with sPHTN (adjusted HR: 1.65; 95% CI: 1.24-2.20) and mPHTN (adjusted HR: 1.44; 95% CI: 1.11-1.85; both P ≤ 0.005) was observed independently of ERO and all baseline characteristics and in all patient subsets. Nested models demonstrated incremental prognostic value of mPHTN and sPHTN (all P < 0.0001). Despite higher operative risk with mPHTN and sPHTN, DMR surgical correction was followed by higher survival in all PHTN ranges with strong survival benefit of early surgery (<3 months). Postoperatively, excess mortality was abolished (P ≥ 0.30) in mPHTN, but only abated in sPHTN. ConclusionsThis large international registry, with prospectively quantified DMR and SPAP, demonstrates a Doppler-defined PHTN impact on mortality, independent of DMR severity. Crucially, it defines objectively the new and frequent mPHTN range, independently linked to excess mortality under medical management, which is abolished by DMR correction. Thus, at DMR diagnosis, Doppler-SPAP measurement defining these new PHTN ranges, is crucial to guiding DMR management.

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.

Fact or Artifact: A prospective study on diagnostic value of a new echocardiographic parameter of Color Doppler Horizontal Splay width in assessment of mitral regurgitation severity

Objective. 1. To evaluate the diagnostic value of the echocardiographic parameter of Color Doppler Horizontal Splay width (CDHSW) in assessment the of mitral regurgitation (MR) severity.2. To determine the cut-off values of CDHSW for the diagnosis of severe MR.Material and methods. A prospective data collection of 81 patients with presence of CDHS on echocardiography was carried out. Transesophageal echocardiography was performed in all of them to clarify the etiology and severity of MR, and in addition, 33 (40%) patients underwent phase-contrast magnetic resonance imaging.Results. After multiparametric examination severe MR was found in 32 (39%) patients, moderate MR in 47 (58%) and mild MR in 2 (3%). Regurgitation jet was eccentric in 79 (98%) patients, and sharply eccentric in 58 (71%) of them. The values of CDHSW (measured in 4-chamber, 2-chamber view, and mean CDHSW values) were significantly higher in the group of severe MR in comparison with the group of moderate MR. A statistically significant strong correlation was revealed between the CDHSW (measured in the 4- and 2-chamber view, and mean CDHSW values) with the values of MR volume, regurgitant fraction, size of effective regurgitant orifice, and a moderate correlation with the values of vena contracta width, left ventricle end-diastolic velocity and left atrium volume. ROC analysis showed the highest diagnostic value (AUC 0,93 ± 0,5, p &lt; 0,001) of mean CDHSW in diagnosis of severe MR in comparison with CDHSW. Optimal cutoff value for mean CDHSW for severe MR diagnosis was &gt;30 mm with a sensitivity of 88% and specificity of 71%.Conclusions. 1. CDHSW is an echocardiographic parameter that provides additional opportunities in the diagnosis of latent moderate and severe eccentric MR.2. It is reasonable to use mean values for the increase of diagnostic sensitivity of CDHSW.3. The mean value of CDHSW &gt;30 mm is highly suggestive to severe MR.

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.

European Association of Cardiovascular Imaging survey on the evaluation of mitral regurgitation.

To evaluate the diagnosis and imaging of patients with mitral regurgitation (MR) and the management in routine clinical practice across Europe, the European Association of Cardiovascular Imaging Scientific Initiatives Committee performed a survey across European centres. In particular, the routine use of echocardiography, advanced imaging modalities, heart valve clinics, and heart valve teams was explored. A total of 61 responders, mainly from tertiary centres or university hospitals, from 26 different countries responded to the survey, which consisted of 22 questions. For most questions related to echocardiography and advanced imaging, the answers were relatively homogeneous and demonstrated good adherence to current recommendations. In particular, the centres used a multi-parametric echocardiographic approach and selected the effective regurgitant orifice and vena contracta width as their preferred assessments. 2D measurements are still the most widely used parameters to assess left ventricular structure; however, the majority use 3D trans-oesophageal echocardiography (TOE) to evaluate valve morphology in severe MR. The majority of centres reported the onsite availability and clinical use of ergometric stress echocardiography, cardiac computed tomography (CCT), and cardiac magnetic resonance (CMR) imaging. Heart valve clinics and heart valve teams were also widely prevalent. Consistent with current guidelines, echocardiography (transthoracic echocardiography and TOE) remains the first-line and central imaging modality for the assessment of MR although the complementary use of 3D TOE, CCT, and CMR appears to be growing. Heart valve clinics and heart valve teams are now widely prevalent.

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.

Annular remodelling predicts outcome in isolated severe tricuspid regurgitation: a registry-based echocardiographic analysis.

Depending on volume status, secondary tricuspid regurgitation (sTR) has a strong dynamic component. In contrast, associated structural dilatation of the tricuspid annulus and the right heart chambers may be less volume dependent. This study aimed to assess the prognostic value of right heart remodelling in isolated severe sTR (isoTR). A total of 36 000 patients from the longitudinal echocardiographic database of our tertiary centre were screened for severe isoTR [vena contracta (VC) ≥ 7 mm] in the absence of atrial fibrillation (AF), other valve disease, and/or reduced systolic left ventricular function. Echocardiographic examinations were re-read, focusing on right ventricular (RV) parameters and on quantitative and qualitative parameters of isoTR. All-cause mortality was defined as the primary endpoint. Two hundred and sixteen patients fulfilled the inclusion criteria. Severe TR was predominant; only few were classified in the new grades massive [n = 23 (10%)] and torrential TR [n = 4 (2%)]. During a median follow-up of 35 months (20-53), all-cause mortality was 31% (n = 67). Multivariate Cox regression analysis revealed no association of VC, effective regurgitant orifice area, or regurgitant volume with all-cause mortality. However, indexed RV end-diastolic diameter (P < 0.001), indexed right atrial dimensions (P = 0.019), and particularly tricuspid valve (TV) annulus diameter diastole index (P = 0.002) and TV annulus diameter systole index (P = 0.001) were significantly associated with outcome. Severe isolated TR in the absence of AF is a rare finding with a grim prognosis. Tricuspid annular diameter dimensions rather than quantitative measures of TR proved to be of significant prognostic value indicating a continuous remodelling leading to a 'point of no return' with a dismal outcome.

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.

Mortality Associated With Proportionality of Secondary Mitral Regurgitation After Transcatheter Mitral Valve Repair: North American Mitraclip for Functional Mitral Regurgitation Registry

The association, if any, between the effective regurgitant orifice area (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients who undergo mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip system (Abbott Vascular, Santa Clara, CA). This study's objective was to determine the association between EROA/LVEDV and 1-year mortality in patients who undergo m-TEER with MitraClip. In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. We studied 525 patients with secondary MR who underwent m-TEER. Most patients were male (63%) and were New York Heart Association class III (61%) or IV (21%). Mitral regurgitation was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely, with median=0.19 mm2/ml, interquartile range [0.12,0.28] mm2/ml, and 187 patients (36%) had values <0.15 mm2/ml. Postprocedural mitral regurgitation severity was substantially alleviated, being 1+ or less in 74%, 2+ in 20%, 3+ in 4%, and 4+ in 2%; 1-year mortality was 22%. After adjustment for confounders, the logarithmic transformation (Ln) of EROA/LVEDV was associated with 1-year mortality (odds ratio 0.600, 95% confidence interval 0.386 to 0.933, p=0.023). A higher Society of Thoracic Surgeons risk score was also associated with increased mortality. In conclusion, lower values of Ln(EROA/LVEDV) were associated with increased 1-year mortality in this multicenter registry. The slope of the association is steep at low values but gradually flattens as Ln(EROA/LVEDV) increases.

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.

Epidemiology and prognostic relevance of morphofunctional classification of secondary mitral regurgitation

Abstract Background Mitral regurgitation has traditionally been divided into organic and functional (FMR) due to its different etiology and prognosis. However, FMR is not a homogeneous entity, and may be secondary to annular dilation, ventricular dilation and dysfunction, or posterior leaflet restriction. Purpose Our aim is to assess the epidemiology of these FMR subtypes and their prognostic impact. Methods Patients with FMR from our center who underwent three-dimensional transesophageal echocardiography (3D-TEE) between 2016 and 2020 were retrospectively evaluated. Patients with at least moderate FMR, effective regurgitant orifice (ERO) by 3D-TEE &amp;gt;0.2 cm2 were selected. They were classified according to the predominant mechanism: type 1 or ventricular dysfunction, type 2 or posterior leaflet restriction, and type 3 or annular dilation. 3D-TEE and the closest transthoracic study variables, as well as baseline demographic and clinical characteristics and evolution events, were obtained and statistical analysis was performed according to FMR types. Results 112 patients were included (66.1% male, mean age 72.3 years). 54.5% had previous hospitalization for heart failure and 53.6% had a history of ischemic heart disease. The most frequently identified FMR mechanism was type 1 (61.6%), followed by type 3 (23.2%) and type 2 (15.2%). There were significant differences in epidemiological factors and echocardiographic parameters (Table) between groups. During follow-up, 43.8% died, received a heart transplant or LVAD and 44.6% had any hospitalization for heart failure. There were no significant differences between FMR types in relation to total mortality (p=0.28), mortality due to heart failure (p=0.13), total hospitalizations (p=0.73), or hospitalization for heart failure (p=0.12). Valvular intervention was performed in 54 patients (48.2%), 33 of them percutaneously with a clip, with no differences in FMR subtypes. Conclusions FMR is a heterogeneous entity and different morphotypes with different epidemiology and etiology can be identified. Despite the different mechanism, all subgroups presented a similar unfavorable prognosis and similar intervention rates.

Prognostic value of three-dimensional regurgitant orifice determination in functional mitral regurgitation

Abstract Background Functional mitral regurgitation (FMR) evaluation using effective regurgitant orifice (ERO) by echocardiography remains controversial. Given the morphology of regurgitant jets in FMR, determination of ERO using three-dimensional transesophageal echocardiography (3D-TEE) may be more accurate. However, a clear threshold for this parameter has not been defined. Purpose Our aim is to evaluate the prognostic value of 3D-ERO in FMR. Methods All patients with at least moderate FMR who underwent 3D-TEE in a tertiary center between 2016 and 2020 were retrospectively selected. Echocardiographic variables by transthoracic and transesophageal, as well as demographic and clinical history variables, were collected. A combined event of urgent hospital admission or death was considered. Variables statistically associated with the event were included in multivariate analysis. Results 112 patients (74 men (66.1%), mean age 72.3±10.9 years) were finally included. The most frequent etiology of FMR was ventricular dysfunction (61.6%), followed by annular dilation (23.2%) and posterior leaflet restriction (15.2%). The mean 3D-ERO was 0.53±0.25 cm2 and mean ejection fraction was 40.7±14.2%. At diagnosis, 49 patients (43.8%) were not receiving diuretics, 63 (56.2%) had atrial fibrillation/flutter, 60.3% permanent. FMR was treated in 54 patients (48.2%), 61,1% percutaneously. During a follow-up of 36 [14-54] months, 50 (44,6%) patients were urgently hospitalized (mean 1.9±2.8 admissions) and 49 (43,8%) died, received a heart transplant or LVAD. 3D-ERO was significantly associated with the occurrence of the event (0.55 vs 0.41; p=0.02). Additionally, 3D-ERO was associated with mitral intervention (0.58 vs 0.47 cm2; p=0.01) and had a trend towards death from any cause (0.56 vs 0.5 cm2; p=0.098). The prognostic capacity of 3D-ERO for the combined event was determined using an ROC curve (Figure). An AUC of 0.67 (95% CI 0.55-0.8; p=0.01) and an optimal cutoff value of 0.45 cm2 (sensitivity 0.62, specificity 0.73) were obtained. In univariate analysis, the combined event was also associated with age (73.9 vs. 65.6 years; p=0.01), diabetes (40 vs. 13.6%; p=0.02), chronic kidney disease (42.7 vs. 13.6%; p=0.01), ischemic heart disease (59.6 vs 31,8%, p=0.02) and daily furosemide dose (39.7 vs. 13.6 mg; p&amp;lt;0.01). In multivariate analysis of the event, age, daily furosemide dose, ischemic heart disease and 3D-ERO were included in the final predictive model (Table). Conclusions In patients with FMR, 3D-ERO was significantly associated with the occurrence of events during follow-up, with an optimal prognostic performance cutoff point of 0.45 cm2. Furthermore, it was an independent predictor of mitral intervention and included among the predictors of urgent hospital admission or death. Therefore, 3D-ERO may be useful in risk stratification of FMR.

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.

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