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Background Hypothesis Animals Methods Results Conclusions and Clinical Importance Reliability of echocardiographic calculations for stroke volume and mitral regurgitant fraction (RFMR) are affected by observer variability and lack of a gold standard. Variability is used to calculate critical change values (CCVs) that are thresholds representing real change in a measure not associated with observer variability.Observed intra‐ and interobserver accuracy and variability in healthy dogs help model CCV for RFMR.Reliability cohort of 34 healthy dogs; allometric scaling cohort of 99 dogs with heart disease and 25 healthy dogs.Accuracy, variability, and CCV of 2 observers using geometric and flow‐based echocardiography were prospectively compared against a standard of RFMR = 0% and extrapolated across a range of expected RFMR values in the reliability cohort partly derived from cardiac dimensions predicted by the allometric cohort.Accuracy of methods to determine RFMR in descending order was 4‐chamber bullet (Bullet4CH), mitral inflow, cube formula, and Simpson's method of disks. Intraobserver variability was relatively high. The CCV for RFMR ranged from 28% to 88% and was inversely related to RFMR when extrapolated for use in affected dogs. For both observers, the Bullet4CH method had the lowest intraobserver CCV (Operator 1:28%, Operator 2:41%). Interobserver strength of agreement was low with intraclass correlation coefficients ranging from 0.210 to 0.413.Echocardiographic volumetric methods used to calculate stroke volume and RFMR have low accuracy and high variability in healthy dogs. Extrapolation of observed CCV to a range of expected RFMR suggests observers and methods are not interchangeable and variability might hinder routine clinical usage. Individual observers should be aware of their own variability and CCV. [ABSTRACT FROM AUTHOR]

Aims 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). Methods and results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Aims The conceptual framework of proportionate vs. disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with 'disproportionate' MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip™ device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial. Methods and results The ratio of pre-procedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH). Among 567 patients, the median RVol/LAV was 0.67 (interquartile range 0.48–0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20–2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (P interaction = 0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group. Conclusion Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio. Clinical Trial Registration Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier NCT01626079 URL https://clinicaltrials.gov/ct2/show/NCT01626079 [ABSTRACT FROM AUTHOR]

A procedure for the treatment of tricuspid regurgitation through membrane insertion has been developed recently. However, membrane optimization is required to balance treatment effectiveness with valve damage. This optimization must be performed based on hemodynamic analyses, using the computational fluid dynamics method. The objectives of this study were to analyze hemodynamic features and provide guidelines for the patient-specific optimization of membranes. We used the lattice Boltzmann method for the base blood flow solver and the immersed boundary method to analyze the interactions among the membrane, leaflet, and blood flow. Optimization was performed by the membrane’s volume and insertion angle, and the effects of the shape and surface contact angle of the membrane were observed. Among various patient-specific features, the annulus ratio, hematocrit, and age were selected as control variables. Hemodynamic features were classified as features related to treatment effectiveness, including the regurgitant volume, jet area, and pressure gradient, and those related to the valve leaflet thickening risk, including the Reynolds shear stress, turbulent kinetic energy, and vorticity magnitude. Our analysis results revealed that treatment effectiveness and leaflet damage have a tradeoff relationship; nevertheless, optimizing certain features such as the membrane shape or surface treatment can reduce damage.

To evaluate regurgitant fraction (RF) using Simpson's method of discs to estimate total stroke volume (RF SMOD_TSV) and using Motion-mode to estimate total stroke volume (RF M-modeTSV) in dogs with subclinical myxomatous mitral valve disease (MMVD). We also sought to evaluate the effects of pimobendan on RF, and to determine the reproducibility of RF SMOD_TSV and RF M-modeTSV. Echocardiography was performed on 57 dogs with MMVD (30 stage B1 and 27 stage B2). Ten dogs received pimobendan for 7–10 days and had a second echocardiogram. Nine dogs underwent six repeated echocardiographic examinations by two operators on three nonconsecutive days within one week for reproducibility analysis. Both RF SMOD_TSV and RF M-modeTSV exhibited a curvilinear relationship with left atrium-to-aortic root ratio. Both RF SMOD_TSV and RF M-modeTSV varied considerably within stage B1 (minimum–maximum: −9.1%–58.2% and −35.7%–66.2%, respectively) and B2 (13.6%–76.2% and 20.1%–85.7%, respectively). Method comparison showed RF SMOD_TSV and RF M-modeTSV were not interchangeable with proportional bias. Pimobendan significantly reduced RF SMOD_TSV (−32.0% ± 23.3%) and RF M-modeTSV (−19.2% ± 10.9%) within the same dog and relative to controls. Good inter-day and between-operator reproducibility was observed for RF SMOD_TSV and RF M-modeTSV based on intraclass correlation coefficients 0.86–0.90 and 0.83–0.90, respectively. Reproducibility coefficients were 19.6%–24.1% and 24.1%–27.0%, respectively. Use of RF using the total stroke volume method to aid the assessment of dogs with subclinical MMVD might be of clinical value. However, further study is warranted. Based on response to pimobendan and reproducibility analysis, RF SMOD_TSV might be a more reliable technique to quantify RF. [ABSTRACT FROM AUTHOR]

The accurate quantification of primary mitral regurgitation (MR) and its consequences on cardiac remodeling is of paramount importance to determine the best timing for surgery in these patients. The recommended echocardiographic grading of primary MR severity relies on an integrated multiparametric approach. It is expected that the large number of echocardiographic parameters collected would offer the possibility to check the measured values regarding their congruence in order to conclude reliably on MR severity. However, the use of multiple parameters to grade MR can result in potential discrepancies between one or more of them. Importantly, many factors beyond MR severity impact the values obtained for these parameters including technical settings, anatomic and hemodynamic considerations, patient's characteristics and echocardiographer' skills. Hence, clinicians involved in valvular diseases should be well aware of the respective strengths and pitfalls of each of MR grading methods by echocardiography. Recent literature highlighted the need for a reappraisal of the severity of primary MR from a hemodynamic perspective. The estimation of MR regurgitation fraction by indirect quantitative methods, whenever possible, should be central when grading the severity of these patients. The assessment of the MR effective regurgitant orifice area by the proximal flow convergence method should be used in a semi-quantitative manner. Furthermore, it is crucial to acknowledge specific clinical situations in MR at risk of misevaluation when grading severity such as late-systolic MR, bi-leaflet prolapse with multiple jets or extensive leak, wall-constrained eccentric jet or in older patients with complex MR mechanism. Finally, it is debatable whether the 4-grades classification of MR severity would be still relevant nowadays, since the indication for mitral valve (MV) surgery is discussed in clinical practice for patients with 3+ and 4+ primary MR based on symptoms, specific markers of adverse outcome and MV repair probability. Primary MR grading should be seen as a continuum integrating both quantification of MR and its consequences, even for patients with presumed “moderate” MR.

A procedure for the treatment of tricuspid regurgitation through membrane insertion has been developed recently. However, membrane optimization is required to balance treatment effectiveness with valve damage. This optimization must be performed based on hemodynamic analyses, using the computational fluid dynamics method. The objectives of this study were to analyze hemodynamic features and provide guidelines for the patient-specific optimization of membranes. We used the lattice Boltzmann method for the base blood flow solver and the immersed boundary method to analyze the interactions among the membrane, leaflet, and blood flow. Optimization was performed by the membrane's volume and insertion angle, and the effects of the shape and surface contact angle of the membrane were observed. Among various patient-specific features, the annulus ratio, hematocrit, and age were selected as control variables. Hemodynamic features were classified as features related to treatment effectiveness, including the regurgitant volume, jet area, and pressure gradient, and those related to the valve leaflet thickening risk, including the Reynolds shear stress, turbulent kinetic energy, and vorticity magnitude. Our analysis results revealed that treatment effectiveness and leaflet damage have a tradeoff relationship; nevertheless, optimizing certain features such as the membrane shape or surface treatment can reduce damage. [ABSTRACT FROM AUTHOR]

Aims In functional tricuspid regurgitation (FTR) patients, tricuspid leaflet tethering and relatively low jet velocity could result in proximal flow geometry distortions that lead to underestimation of TR. Application of correction factors on two-dimensional (2D) proximal isovelocity surface area (PISA) equation may increase its reliability. This study sought to evaluate the impact of the corrected 2D PISA method in quantifying FTR severity. Methods and results In 102 patients with FTR, we compared both conventional and corrected 2D PISA measurements of effective regurgitant orifice area [EROA vs. corrected (EROAc)] and regurgitant volume (RegVol vs. RegVolc) with those obtained by volumetric method (VM) using three-dimensional echocardiography (3DE), as reference. Both EROAc and RegVolc were larger than EROA (0.29 ± 0.26 vs. 0.22 ± 0.21 cm2; P < 0.001) and RegVol (24.5 ± 20 vs. 18.5 ± 14.25 mL; P < 0.001), respectively. Compared with VM, both EROAc and RegVolc resulted more accurate than EROA [bias = −0.04 cm2, limits of agreement (LOA) ± 0.02 cm2 vs. bias = −0.15 cm2, LOA ± 0.31 cm2] and RegVol (bias = −3.29 mL, LOA ± 2.19 mL vs. bias = −10.9 mL, LOA ± 13.5 mL). Using EROAc and RegVolc, 37% of patients were reclassified in higher grades of FTR severity. Corrected 2D PISA method led to a higher concordance of TR severity grade with the VM method (ĸ = 0.84 vs. ĸ = 0.33 for uncorrected PISA, P < 0.001). Conclusion Compared with VM by 3DE, the conventional PISA underestimated FTR severity in about 50% of patients. Correction for TV leaflets tethering angle and lower velocity of FTR jet improved 2D PISA accuracy and reclassified more than one-third of the patients. [ABSTRACT FROM AUTHOR]

Grading of aortic regurgitation (AR) and mitral regurgitation (MR) is similar in the cardiology guidelines despite distinct differences in left ventricular (LV) adaptive pathophysiology. This study compared differences in LV remodeling in patients with similar degrees of AR and MR severity and evaluated optimal cutoffs for significant AR in relation to the outcome of aortic valve replacement or repair (AVR) during follow-up. From 2008 to 2018, consecutive patients with isolated AR or MR who had cardiac magnetic resonance (CMR) were identified and CMR parameters were compared. Patients with left ventricular ejection fraction (LVEF) <50%, ischemic scar >5%, valve stenosis, or concomitant regurgitation were excluded. Patients were followed longitudinally for AVR. Baseline characteristics of isolated AR (n = 418) and isolated MR (n = 1,073) were comparable except for higher male proportion and hypertension in AR, while heart failure was more prevalent in MR. Indexed LV end-diastolic and end-systolic volumes and mass were higher in AR compared with MR at the same level of regurgitant fraction. During follow-up (mean 2.1 years), 18.7% of AR patients underwent AVR based on symptoms or LV remodeling. Interestingly, 38.0% of patients that underwent AVR within 3 months after CMR did not meet severe AVR by current guidelines of AR severity. AR regurgitant fraction>35% had high sensitivity (86%) and specificity (88%) for identifying patients who underwent AVR. For similar regurgitation severity, LV remodeling is different in AR compared with MR. Cardiac symptoms and significant LV remodeling in AR requiring AVR occur frequently in patients with less severity than currently proposed. The study findings suggest that the optimal threshold for severe AR with CMR is different than MR and is lower than currently stated in the guidelines. [Display omitted] [ABSTRACT FROM AUTHOR]

Valvular regurgitation is common in developed countries with an increasing prevalence due to the aging of the population and more accurate diagnostic imaging methods. Echocardiography is the gold standard method for the assessment of the severity of valvular heart regurgitation. Nonetheless, cardiovascular magnetic resonance (CMR) has emerged as an additional tool for assessing mainly the severity of aortic and mitral valve regurgitation in the setting of indeterminate findings by echocardiography. Moreover, CMR is a valuable imaging modality to assess ventricular volume and flow, which are useful in the calculation of regurgitant volume and regurgitant fraction of mitral valve regurgitation, aortic valve regurgitation, tricuspid valve regurgitation, and pulmonary valve regurgitation. Notwithstanding this, reference values and optimal thresholds to determine the severity and prognosis of valvular heart regurgitation have been studied lesser by CMR than by echocardiography. Hence, further larger studies are warranted to validate the potential prognostic relevance of the severity of valvular heart regurgitation determined by CMR. The present review describes, analyzes, and discusses the use of CMR to determine the severity of valvular heart regurgitation in clinical practice.

Purpose: The purpose of this study was to evaluate the accuracy of four‐dimensional (4D) flow MRI for direct assessment of peak velocity, flow volume, and momentum of a mitral regurgitation (MR) flow jets using an in vitro pulsatile jet flow phantom. We systematically investigated the impact of spatial resolution and quantification location along the jet on flow quantities with Doppler ultrasound as a reference for peak velocity. Methods: Four‐dimensional flow MRI data of a pulsatile jet through a circular, elliptical, and 3D‐printed patient‐specific MR orifice model was acquired with varying spatial resolution (1.5–5 mm isotropic voxel). Flow rate and momentum of the jet were quantified at various axial distances (x = 0–50 mm) and integrated over time to calculate Voljet and MTIjet. In vivo assessment of Voljet and MTIjet was performed on 3 MR patients. Results: Peak velocities were comparable to Doppler ultrasound (3% error, 1.5 mm voxel), but underestimated with decreasing spatial resolution (−40% error, 5 mm voxel). Voljet was similar to regurgitant volume (RVol) within 5 mm, and then increased linearly with the axial distance (19%/cm) because of flow entrainment. MTIjet remained steady throughout the jet (2%/cm) as theoretically predicted. Four and 9 voxels across the jet were required to measure flow volume and momentum‐time‐integral within 10% error, respectively. Conclusion: Four‐dimensional flow MRI detected accurate peak velocity, flow rate, and momentum for in vitro MR‐mimicking flow jets. Spatial resolution significantly impacted flow quantitation, which otherwise followed predictions of flow entrainment and momentum conservation. This study provides important preliminary information for accurate in vivo MR assessment using 4D flow MRI. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the feasibility and accuracy of chronic aortic regurgitation (CAR) quantification using left and right ventricular stroke volumes (LVSV and RVSV, respectively) obtained from two new automated three-dimensional transthoracic echocardiographic software—Dynamic HeartModel (DHM) and 3D Auto RV. Patients (n=116) with more than mild isolated CAR were included and divided into two groups: central (n=53) and eccentric CAR (n=63) groups. LVSV and RVSV were automatically measured by DHM and 3D Auto RV. Next, aortic regurgitant volume (ARVol) was calculated three ways: as the difference between LVSV and RVSV, by the two-dimensional proximal isovelocity surface area (PISA) method, and using effective regurgitant orifice area derived from real-time three-dimensional echocardiography (RT3DE) multiplied by CAR velocity time integral (the reference standard). DHM plus 3D Auto RV correlated well with RT3DE in ARVol measurement in both groups (central, r = 0.90; eccentric, r = 0.96), with no significant difference based on consistency analysis. In the eccentric group, PISA led to an obvious underestimation (mean difference= − 4.20 ml, P < 0.05). The kappa agreement between DHM plus 3D Auto RV and RT3DE in grading CAR severity in both groups was good (central, k = 0.89; eccentric, k = 0.86), but that between PISA and RT3DE in the eccentric CAR group was suboptimal (k = 0.74). This study indicates that ARVol quantification using DHM plus 3D Auto RV is feasible and reproducible in patients with more than mild isolated CAR. This new method has great correlation and agreement with RT3DE in ARVol measurement, with evident advantages over PISA in eccentric CAR. [ABSTRACT FROM AUTHOR]

Guidelines suggest using a regurgitant fraction of 50% and regurgitant volume of 60 ml for determination of severe mitral insufficiency. Recent MRI data has suggested that a regurgitant fraction of 40% defines severe primary mitral insufficiency. We sought to determine whether there were gender differences in primary mitral regurgitant volumes for regurgitant fractions of 40% and 50%. A database search identified 394 patients that had MRI with a mitral regurgitant volume ≥ 10 ml or a study indication of mitral insufficiency. Chart review identified 97 patients with primary mitral insufficiency. Of these patients, 53 (54%) were women. Men had significantly larger left ventricular volumes, myocardial mass, stroke volumes and mitral regurgitant volumes (37 ± 25 ml vs. 24 ± 12 ml). The difference in regurgitant fraction between genders was not significant (27 ± 14% vs. 24 ± 11%; p-value = 0.24). Regurgitant fraction and regurgitant volume had a strong linear correlation in both men (r =.95) and women (r =.92). Despite similar linear correlations, the slope-intercept equations differed significantly between men and women (p <.001). A regurgitant fraction of 40% correlated with a regurgitant volume of 59 ml in men and 39.5 ml in women, while a regurgitant fraction of 50% correlated with a regurgitant volume of 76.2 ml in men and 49.6 ml in women. Regurgitant fraction, determined by cardiac MRI, provides a gender independent assessment of primary mitral insufficiency, and suggests that regurgitant volume thresholds for severe primary mitral insufficiency may be lower in women. [ABSTRACT FROM AUTHOR]

Aims: 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)., Methods and Results: 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., Conclusion: 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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

[Display omitted] [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the prognostic implications of the ratio of mitral regurgitant volume (RVol) to left ventricular (LV) end-diastolic volume (EDV) in patients with significant secondary mitral regurgitation (MR). Quantification of secondary MR remains challenging, and its severity can be over- or underestimated when using the proximal isovelocity surface area method, which does not take LV volume into account. This limitation can be addressed by normalizing mitral RVol to LVEDV. A total of 379 patients (mean age 67 ± 11 years; 63% male) with significant (moderate and severe) secondary MR were divided into 2 groups according to the RVol/EDV ratio: RVol/EDV ≥20% (greater MR/smaller EDV) and <20% (smaller MR/larger EDV). The primary endpoint was all-cause mortality. During median (interquartile range) follow-up of 50 (26 to 94) months, 199 (52.5%) patients died. When considering patients receiving medical therapy only, patients with RVol/EDV ratio ≥20% tended to have higher mortality rates than those with RVol/EDV ratio <20% (5-year estimated rates 24.1% vs. 18.4%, respectively; p = 0.077). Conversely, when considering the entire follow-up period including mitral valve interventions, patients with a higher RVol/EDV ratio (≥20%) had lower rates of all-cause mortality compared with patients with RVol/EDV ratio <20% (5-year estimated rates 39.0% vs. 44.8%, respectively; p = 0.018). On multivariable analysis, higher RVol/EDV ratio (per 5% increment as a continuous variable) was independently associated with lower all-cause mortality (0.93; p = 0.023). In patients with significant secondary MR treated medically, survival tended to be lower in those with a higher RVol/EDV ratio. Conversely, a higher RVol/EDV ratio was independently associated with reduced all-cause mortality. when mitral valve interventions were taken into consideration [Display omitted] [ABSTRACT FROM AUTHOR]

Aims Quantitative echocardiography parameters are seldom used to grade tricuspid regurgitation (TR) severity due to relative paucity of validation studies and lack of prognostic data. To assess the relationship between TR severity and the composite endpoint of death and hospitalization for congestive heart failure (CHF); and to identify the threshold values of vena contracta width (VCavg), effective regurgitant orifice area (EROA), regurgitant volume (RegVol), and regurgitant fraction (RegFr) to define low, intermediate, and high-risk TR based on patients' outcome data. Methods and results A cohort of 296 patients with at least mild TR underwent 2D, 3D, and Doppler echocardiography. We built statistical models (adjusted for age, NYHA class, left ventricular ejection fraction, and pulmonary artery systolic pressure) for VCavg, EROA, RegVol, and RegFr to study their relationships with the hazard of outcome. The tertiles of the derived hazard values defined the threshold values of the quantitative parameters for TR severity grading. During 47-month follow-up, 32 deaths and 72 CHF occurred. Event-free rate was 14%, 48%, and 93% in patients with severe, moderate, and mild TR, respectively. Severe TR was graded as VCavg > 6 mm, EROA > 0.30 cm2, RegVol > 30 mL, and RegF > 45%. Conclusion This outcome study demonstrates the prognostic value of quantitative parameters of TR severity and provides prognostically meaningful threshold values to grade TR severity in low, intermediate, and high risk. [ABSTRACT FROM AUTHOR]

Aims: The conceptual framework of proportionate vs. disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with 'disproportionate' MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip™ device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial., Methods and Results: The ratio of pre-procedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH). Among 567 patients, the median RVol/LAV was 0.67 (interquartile range 0.48-0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20-2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (Pinteraction = 0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group., Conclusion: Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio., Clinical Trial Registration: Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier NCT01626079URL https://clinicaltrials.gov/ct2/show/NCT01626079., Competing Interests: Conflict of interest: A.C. has served as a consultant for Abbott and received speaker fees from Abbott and GE Healthcare. A.S. has served as a consultant and received consulting fees from NeoChord Inc. J.F.G. is the co-founder of Cephea Valve Technologies (Abbott). P.A.G. has received consulting fees from Abbott Vascular, Edwards Lifesciences, W.L. Gore, Medtronic, and 4C Medical and has received grant support from Abbott Vascular, Boston Scientific, Cardiovalve, Edwards Lifesciences, W.L. Gore, Medtronic, and Neochord. M.J.M. served as co-primary investigator for the PARTNER Trial for Edwards Lifesciences and COAPT trial for Abbott; served as study chair for the APOLLO trial for Medtronic; all activities unpaid. D.J.C. has received institutional research grants and consulting fees from Abbott, Edwards LifeSciences, Medtronic, and Boston Scientific. S.K. has received grants from Abbott, Boston Scientific, Edwards Lifesciences, and 4TECH; has been a consultant for Boston Scientific, Edwards Lifesciences, Medtronic, and 4TECH; and holds stock options in 4TECH. D.S.L. has received research grant support from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, Trisol, and V Wave; consultant fees from Ancora, Philips, Valgen, and Venus. J.L. has received research grant support from AstraZeneca; consulting income from Abbott Vascular, Alleviant, AstraZeneca, Cordio, CVRx, Edwards Lifesciences, Boehringer Ingelheim, Merck, Medtronic, Vascular Dynamics, and V-Wave. J.B.’s institution has received research grants from Medtronic, Biotronik, Edwards Lifesciences, and Boston Scientific; he has also received speaker fees from Abbott Vascular. F.M.A. and N.J.W. report institutional contracts with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. G.W.S. has received speaker honoraria from Medtronic, Pulnovo, Infraredx, and Abiomed; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. G.W.S.’s daughter is an employee at IQVIA. Institutional disclosure: G.W.S.’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc., Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. The other authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: 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., Methods: We included 229 patients (70 ± 13 years, 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., Results: After a mean follow-up of 20 ±11 months, 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 2 years compared to PISA and 2DEVM (P < .05 for all). Kaplan-Meier analysis demonstrated a significantly higher rate of events in patients with EROA ≥ 0.3 cm 2 (cumulative survival at 2 years: 28% ± 7% vs 32% ± 10% vs 30% ± 11%) and RegVol ≥ 45 mL (cumulative survival at 2 years: 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)., Conclusions: 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., Competing Interests: Conflicts of Interest Dr. Muraru and Dr. Badano are members of the speaker bureaus of GE Healthcare and Philips Medical Systems and received research grants from GE Healthcare, Philips Medical Systems, TomTec Imagng Systems, and ESaOTE SpA. The remaining authors have nothing to disclose., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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Background: Diverging guideline definitions for the quantitative assessment of severe secondary mitral regurgitation (sMR) reflect the lacking link of the sMR spectrum to mortality and has introduced a source of uncertainty and continuing debate.Objectives: The current study aimed to define improved risk-thresholds specifically tailored to the complex nature of sMR that provide a unifying solution to the ongoing guideline-controversy.Methods: This study enrolled 423 heart failure patients under guideline-directed medical therapy and assessed sMR by effective regurgitant orifice area (EROA), regurgitant volume (RegVol), and regurgitant fraction (RegFrac).Results: Measures of sMR severity were consistently associated with 5-year mortality with a hazard ratio of 1.42 for a 1-SD increase (95% confidence interval [CI]: 1.25 to 1.63; p < 0.001) for EROA, 1.37 (95% CI: 1.20 to 1.56; p < 0.001) for RegVol, and 1.50 (95% CI: 1.30 to 1.73; p < 0.001) for RegFrac. Results remained statistically significant after bootstrap- or clinical confounder-based adjustment. Spline-curve analyses showed a linearly increasing risk enabling the ability to stratify into low-risk (EROA <20 mm2 and RegVol <30 ml), intermediate-risk (EROA 20 to 29 mm2 and RegVol 30 to 44 ml), and high-risk (EROA ≥30 mm2 and RegVol ≥45 ml) groups. In the intermediate-risk group, a RegFrac ≥50% as indicator for hemodynamic severe sMR was associated with poor outcome (p = 0.017). A unifying concept based on combined assessment of the EROA, the RegVol, and the RegFrac showed a significantly better discrimination compared with the currently established algorithms.Conclusions: Risk-based thresholds tailored to the pathophysiological concept of sMR provide a unifying solution to the ongoing guideline controversy. An algorithm based on the combined assessment of the unifying cutoffs for EROA, RegVol, and RegFrac improves risk prediction compared with currently established grading. [ABSTRACT FROM AUTHOR]

Abstract Objectives This study sought to define the relationship between functional tricuspid regurgitation (TR) and mortality in patients with heart failure with reduced ejection fraction (HFrEF); and to establish the prognostic value of quantitative measures of TR severity (i.e., effective regurgitant orifice area [EROA] and regurgitant volume). Background The significance of TR in chronic heart failure is controversial. Earlier studies have shown an independent impact of TR on mortality, whereas more recent evidence suggests myocardial impairment to be the driving force of mortality rather than TR itself. Earlier studies have used qualitative measures of TR severity, hence the prognostic value of more quantitative measures of TR severity (i.e., EROA and regurgitant volumes) remains unclear. Methods We enrolled 382 patients with HFrEF on guideline-directed medical therapy and assessed TR EROA and regurgitant volume by Doppler/2-dimensional echocardiography. All-cause mortality was defined as the primary study endpoint. Results TR severity was associated with the HFrEF phenotype with more symptoms (p = 0.004), higher neurohumoral activation (p < 0.001), progressive right-ventricular dilatation (p < 0.001), and impaired function (p < 0.001). Cox regression showed a strong association between quantitative measures of TR with mortality (all p < 0.001). Quantitative metrics of TR severity were consistently associated with mortality with a hazard ratio of 1.009 (95% confidence interval: 1.004 to 1.013; p < 0.001) per 0.01 cm2 increase of the EROA and of 1.013 (95% confidence interval: 1.007 to 1.020; p < 0.001) per 1-ml increase in regurgitant volume. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. A spline curve pattern illustrates the association with mortality with thresholds for the EROA ≥0.2 cm2, and the regurgitant volume ≥20 ml with sustained excess mortality thereafter. Conclusions This large-scale outcome study demonstrates the prognostic value of quantitative Doppler-echocardiographic measures of TR severity in HFrEF. The thresholds for EROA and TR regurgitant volume associated with mortality in our study fall within current ranges defining nonsevere TR. This may potentially impact therapeutic decision making, particularly timing of intervention. Graphical abstract [ABSTRACT FROM AUTHOR]

Mitral regurgitation (MR) is one of the most commonly encountered valvular lesions in clinical practice. MR can be either primary (degenerative) or secondary (functional) depending on the etiology of MR and the pathology of the mitral valve (MV). Echocardiography is the primary diagnostic tool for MR and is key in determining this etiology as well as MR severity. While clinicians usually turn to 2 Dimensional echocardiography as first-line imaging, 3 Dimensional echocardiography (3DE) has continually shown to be superior in terms of describing MV anatomy and pathology. This review article elaborates on 3DE techniques, modalities, and advances in software. Furthermore, the article demonstrates how 3DE has reformed MR evaluation and has played a vital role in determining patient management. [ABSTRACT FROM AUTHOR]

To test the feasibility of assessing mitral regurgitation (MR) severity using cardiac magnetic resonance (CMR) 4D velocity vectors to quantify regurgitant volume (RVol) by analysis of the proximal flow convergence, compared to Doppler based proximal isovelocity surface area (PISA) and CMR volume-based methods. In a prospectively designed study, 27 patients with various grades of MR underwent CMR and echo-Doppler on the same day. By CMR, multiple slices were obtained parallel to the mitral valve by phase-contrast imaging, using 3D velocity vectors, as well as short-axis cine images for left and right ventricular volume measurements. Using dedicated software developed in our laboratory, the perimeter of the proximal flow convergence region was semi-automatically measured for each temporal phase, and for each short-axis slice. The CMR-PISA RVol was calculated as the sum of PISA perimeters throughout systole, multiplied by slice width. For comparison, CMR-volumetric RVol was calculated by 2 methods: Volumetric (difference between left and right ventricular stroke volumes) and Flow-based (stroke volume -aortic flow). Echo-PISA RVol was calculated by echo-Doppler based PISA method. RVol by CMR-PISA correlated highly with echo-PISA (r = 0.87) and with CMR-volumetric (r = 0.86) and CMR-flow (r = 0.72). For comparison Doppler-RVol and CMR-volume-based RVol had r = 0.83. On average CMR-PISA was 16 ± 25 ml less than echo-PISA, but 12 ± 22 ml larger than CMR-volumetric RVol. The observed 3D shape of the PISA envelope by 4D-CMR resembled a hemiellipsoid rather than a hemisphere. This feasibility study suggests that CMR-based 4D-PISA may be able to assess MR severity quantitatively without any geometric assumptions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Overestimation of the severity of mitral regurgitation (MR) by the proximal isovelocity surface area (PISA) method has been reported. We sought to test whether angle correction (AC) of the constrained flow field is helpful to eliminate overestimation in patients with eccentric MR. METHODS: In a total of 33 patients with MR due to prolapse or flail mitral valve, both echocardiography and cardiac magnetic resonance image (CMR) were performed to calculate regurgitant volume (RV). In addition to RV by conventional PISA (RVPISA), convergence angle (α) was measured from 2-dimensional Doppler color flow maps and RV was corrected by multiplying by α/180 (RVAC). RV measured by CMR (RVCMR) was used as a gold standard, which was calculated by the difference between total stroke volume measured by planimetry of the short axis slices and aortic stroke volume by phase-contrast image. RESULTS: The correlation between RVCMR and RV by echocardiography was modest [RVCMR vs. RVPISA (r = 0.712, p < 0.001) and RVCMR vs. RVAC (r = 0.766, p < 0.001)]. However, RVPISA showed significant overestimation (RVPISA - RVCMR = 50.6 ± 40.6 mL vs. RVAC - RVCMR = 7.7 ± 23.4 mL, p < 0.001). The overall accuracy of RVPISA for diagnosis of severe MR, defined as RV ≥ 60 mL, was 57.6% (19/33), whereas it increased to 84.8% (28/33) by using RVAC (p = 0.028). CONCLUSION: Conventional PISA method tends to provide falsely large RV in patients with eccentric MR and a simple geometric AC of the proximal constraint flow largely eliminates overestimation. [ABSTRACT FROM AUTHOR]

Objective To assess differences in mitral regurgitation (MR) grade between the preoperative and the intraoperative evaluations. Design Systematic review and meta-analysis of 6 observational studies found from MEDLINE and EMBASE. Setting Cardiac surgery. Participants One hundred thirty-seven patients. Intervention Comparison between the preoperative MR assessment and the intraoperative evaluation conducted under general anesthesia (GA), with or without “hemodynamic matching” (HM) (artificial increase of afterload). Measurements and Main Results The primary outcome was the difference between the preoperative and intraoperative MR grade under “GA-only” or “after-HM.” Secondary analyses addressed differences according to effective regurgitant orifice area (EROA), regurgitant volume (RVol), color-jet area, and vena contracta width. Risk of MR underestimation was found under “GA-only” (SMD: 0.55; 95% confidence interval [CI], 0.31–0.79, p < 0.00001), but not “after-HM” (SMD: –0.16; 95% CI, –0.46 to 0.13, p = 0.27). Under “GA-only”, EROA had a trend toward underestimation (p = 0.07), RVol was reliable (p = 0.17), while reliance on color-jet area and vena contracta width incur risk of underestimation (both p = 0.003). After HM, EROA accurately reflected preoperative MR (p = 0.68) while RVol had a trend toward overestimation (p = 0.05). The overall reported incidence of misdiagnoses was slightly more common under “GA-only” (mean 48%, 39% underestimation, 9% overestimation; range: 32%–57%) than “after-HM” (mean 41%, 12% underestimation, 29% overestimation; range: 33%–50%). Only the minority of misdiagnoses were clinically relevant: underestimation was around 10% (both approaches), but 18% had clinically significant overestimation “after-HM” as compared with 3% under GA-only. Conclusions Intraoperative assessment under “GA-only” significantly underestimated MR. A more accurate intraoperative evaluation can be obtained with afterload manipulation, although HM strategy carries high risk of clinically significant overestimation. [ABSTRACT FROM AUTHOR]

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