Disproportionate Mitral Regurgitation Determines Survival in Acute Heart Failure

Objectives: To assess the prevalence and impact of mitral regurgitation (MR) on survival in patients presenting to hospital in acute heart failure (AHF) using traditional echocardiographic assessment alongside more novel indices of proportionality.Background: It remains unclear if the severity of MR plays a significant role in determining outcomes in AHF. There is also uncertainty as to the clinical relevance of indexing MR to left ventricular volumes. This concept of disproportionality has not been assessed in AHF.Methods: A total of 418 consecutive patients presenting in AHF over 12 months were recruited and followed up for 2 years. MR was quantitatively assessed within 24 h of recruitment. Standard proximal isovelocity surface area (PISA) and a novel proportionality index of effective regurgitant orifice/left ventricular end-diastolic volume (ERO/LVEDV) >0.14 mm2/ml were used to identify severe and disproportionate MR.Results: Every patient had MR. About 331/418 (78.9%) patients were quantifiable by PISA. About 165/418 (39.5%) patients displayed significant MR. A larger cohort displayed disproportionate MR defined by either a proportionality index using ERO/LVEDV > 0.14 mm2/ml or regurgitant volumes/LVEDV > 0.2 [217/331 (65.6%) and 222/345 (64.3%), respectively]. The LVEDV was enlarged in significant MR−129.5 ± 58.95 vs. 100.0 ± 49.91 ml in mild, [p < 0.0001], but remained within the normal range. Significant MR was associated with a greater mortality at 2 years {44.2 vs. 34.8% in mild MR [hazard ratio (HR) 1.39; 95% CI: 1.01–1.92, p = 0.04]}, which persisted with adjustment for comorbid conditions (HR; 1.43; 95% CI: 1.04–1.97, p = 0.03). Disproportionate MR defined by ERO/LVEDV >0.14 mm2/ml was also associated with worse outcome [42.4 vs. 28.3% (HR 1.62; 95% CI 1.12–2.34, p = 0.01)].Conclusions: MR was a universal feature in AHF and determines outcome in significant cases. Furthermore, disproportionate MR, defined either by effective regurgitant orifice (ERO) or volumetrically, is associated with a worse prognosis despite the absence of adverse left ventricular (LV) remodeling. These findings outline the importance of adjusting acute volume overload to LV volumes and call for a review of the current standards of MR assessment.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02728739, identifier NCT02728739.

Computational analysis of quantitative echocardiographic assessments of functional mitral regurgitation: Proximal Isovelocity Surface Area (PISA) methods

While proximal isovelocity surface area (PISA) method is one of the most common echocardiographic methods for quantitative mitral regurgitation (MR) assessment, accurate MR quantification remains challenging. This study examined the theoretical background of PISA, performed virtual echocardiography on computer models of functional MR, and quantified different sources of errors in PISA. For regurgitant flow rate measurement, the conventional 2D hemispherical PISA caused significant underestimation due to underestimation of PISA area, the multiplane 2D hemiellipsoidal and hemicylindrical PISA provided improved accuracy with better assumptions on PISA contour shape. With the direct capture of PISA area, the 3D-PISA was found to be the most accurate. However, it should be noted that PISA method is subject to systematic underestimation due to the Doppler angle effect, and systematic overestimation due to the “flow direction angle” between the regurgitant flow direction and the PISA contour normal direction. For regurgitant volume quantification, integrated PISA, when performed properly, was able to capture the dynamic MR and therefore was more accurate than peak PISA. In specific, integrated PISA using the sum of regurgitant flow rates is recommended.ObjectivesThe aim of this study was to evaluate the accuracy of different proximal isovelocity surface area (PISA) methods, examine their theoretical background, and quantify multiple sources of error in functional mitral regurgitation (MR) assessment.BackgroundWhile PISA method is one of the most common echocardiographic methods for MR severity assessment, it is associated with multiple sources of errors, and accurate MR quantification remains challenging.MethodsFive functional MR (FMR) computer models were created, validated and treated as phantom models. The phantom models have fully resolved and detailed flow fields in the left atrium (LA), left ventricle (LV) and cross the mitral valve, from which the reference values of mitral regurgitant flow rate and regurgitant volume can be obtained. The virtual PISA measurements (i.e., 3D and 2D PISA) were performed on the phantom models assuming optimal echo probe angulation and positioning. The results of different PISA methods were compared with the reference values.ResultsFor regurgitant flow rate measurements, compared to the reference values, excellent correlations were observed for 3D-PISA (R = 0.97, bias -24.4 ± 55.5 ml/s), followed by multiplane 2D hemicylindrical (HC)-PISA (R = 0.88, bias -24.1 ± 85.4 ml/s) and hemiellipsoidal (HE)-PISA (R = 0.91, bias -55.7 ± 96.6 ml/s), while weaker correlations were observed for single plane 2D hemispherical (HS)-PISA with large underestimation (PLAX view: R = 0.71, bias -77.6 ± 124.5 ml/s; A2Ch view: R = 0.69, bias -52.0 ± 122.0 ml/s; A4Ch view: R = 0.82, bias -65.5 ± 107.3 ml/s). For regurgitant volume (RV) quantification, integrated PISA presented improved accuracy over peak PISA for all PISA methods. For 3D-PISA, the bias in RV improved from -12.7 ± 7.8 ml (peak PISA) to -2.1 ± 5.3 ml (integrated PISA).ConclusionsIn FMR, conventional single plane 2D HS-PISA significantly underestimated MR, multiplane 2D PISA (HE-PISA and HC-PISA) improved the accuracy, and 3D-PISA is the most accurate. To better capture the dynamic feature of MR, integrated PISA using the sum of regurgitant flow rates is recommended.

Anatomical and Hemodynamic Evaluation of Mitral Stenosis Patients with Echocardiography

Mitral stenosis (MS) is the most common valvular heart disease encountered in developing countries. The cause of MS is almost always chronic rheumatic heart disease. Echocardiography is the single most important diagnostic tool in the evaluation of MS. The objectives are to confirm the etiology, to assess the severity of stenosis, to recommend the type and timing of intervention, to assess other valvular lesions, presence of thrombus, and vegetation. According to current guidelines and recommendations for clinical practice, the severity of MS should not be defined by a single value but rather be assessed by a multimodality approach that determines valve areas, mean Doppler gradients, and pulmonary arterial pressures. The European Society of Echocardiography/American Society of Echocardiography (EAE/ASE) recommendations of measurement method for clinical practice were categorized into three level of recommendations. Mitral valve area (MVA) can be assessed by planimetry using either 2D or 3D imaging, pressure half-time (PTH), the continuity equation, and the proximal isovelocity surface area (PISA) method. These result echocardiographic examinations can increase the accuracy and appropriate management with a good prognosis.

Quantification of regurgitation in mitral valve prolapse with four-dimensional flow cardiovascular magnetic resonance

Background Four-dimensional cardiovascular magnetic resonance (CMR) flow assessment (4D flow) allows to derive volumetric quantitative parameters in mitral regurgitation (MR) using retrospective valve tracking. However, prior studies have been conducted in functional MR or in patients with congenital heart disease, thus, data regarding the usefulness of 4D flow CMR in case of a valve pathology like mitral valve prolapse (MVP) are scarce. This study aimed to evaluate the clinical utility of cine-guided valve segmentation of 4D flow CMR in assessment of MR in MVP when compared to standardized routine CMR and transthoracic echocardiography (TTE). Methods Six healthy subjects and 54 patients (55 ± 16 years; 47 men) with MVP were studied. TTE severity grading used a multiparametric approach resulting in mild/mild-moderate (n = 12), moderate-severe (n = 12), and severe MR (n = 30). Regurgitant volume (RVol) and regurgitant fraction (RF) were also derived using standard volumetric CMR and 4D flow CMR datasets with direct measurement of regurgitant flow (4DFdirect) and indirect calculation using the formula: mitral valve forward flow - left ventricular outflow tract stroke volume (4DFindirect). Results There was moderate to strong correlation between methods (r = 0.59–0.84, p < 0.001), but TTE proximal isovelocity surface area (PISA) method showed higher RVol as compared with CMR techniques (PISA vs. CMR, mean difference of 15.8 ml [95% CI 9.9–21.6]; PISA vs. 4DFindirect, 17.2 ml [8.4–25.9]; PISA vs. 4DFdirect, 27.9 ml [19.1–36.8]; p < 0.001). Only indirect CMR methods (CMR vs. 4DFindirect) showed moderate to substantial agreement (Lin’s coefficient 0.92–0.97) without significant bias (mean bias 1.05 ± 26 ml [− 50 to 52], p = 0.757). Intra- and inter-observer reliability were good to excellent for all methods (ICC 0.87–0.99), but with numerically lower coefficient of variation for indirect CMR methods (2.5 to 12%). Conclusions In the assessment of patients with MR and MVP, cine-guided valve segmentation 4D flow CMR is feasible and comparable to standard CMR, but with lower RVol when TTE is used as reference. 4DFindirect quantification has higher intra- and inter-technique agreement than 4DFdirect quantification and might be used as an adjunctive technique for cross-checking MR quantification in MVP.

Optimal Quantification of Functional Mitral Regurgitation: Comparison of Volumetric and Proximal Isovelocity Surface Area Methods to Predict Outcome

Background Effective orifice area (EOA) ≥0.2 cm 2 or regurgitant volume (Rvol) ≥30 mL predicts prognostic significance in functional mitral regurgitation (FMR). Both volumetric and proximal isovelocity surface area (PISA) methods enable calculation of these metrics. To determine their clinical value, we compared EOA and Rvol derived by volumetric and PISA quantitation upon outcome of patients with FMR. Methods and Results We examined the outcome of patients with left ventricular ejection fraction <35% and moderate to severe FMR. All had a complete echocardiogram including EOA and Rvol by both standard PISA and volumetric quantitation using total stroke volume calculated by left ventricular end‐diastolic volume×left ventricular ejection fraction and forward flow by Doppler method: EOA=Rvol/mitral regurgitation velocity time integral. Primary outcome was all‐cause mortality or heart transplantation. We examined 177 patients: mean left ventricular ejection fraction 25.2% and 34.5% with ischemic cardiomyopathy. Echo measurements were greater by PISA than volumetric quantitation: EOA (0.18 versus 0.11 cm 2 ), Rvol (24.7 versus 16.9 mL), and regurgitant fraction (61 versus 37 %) respectively (all P value <0.001). During 3.6±2.3 years’ follow‐up, patients with EOA ≥0.2 cm 2 or Rvol ≥30 mL had a worse outcome than those with EOA <0.2 cm 2 or Rvol <30 mL only by volumetric (log rank P =0.003 and 0.004) but not PISA quantitation (log rank P =0.984 and 0.544), respectively. Conclusions Volumetric and PISA methods yield different measurements of EOA and Rvol in FMR; volumetric values exhibit greater prognostic significance. The echo method of quantifying FMR may affect the management of this disorder.

Application of the Proximal Isovelocity Surface Area Method for Estimation of the Effective Orifice Area in Aortic Stenosis

Purpose: Because existence of high flow velocity at the left ventricular outflow tract (LVOT) potentially causes an overestimation of effective orifice area (EOA) by continuity equation in aortic stenosis (AS), we tested the proximal isovelocity surface area (PISA) method as an alternative tool for AS.Methods: EOA was calculated using the continuity equation (EOACont) and PISA method (EOAPISA), respectively, in 114 patients with at least moderate AS. The geometric orifice area (GOA) was also measured in 51 patients who also underwent three-dimensional transesophageal echocardiography (TEE). Patients were divided into two groups according to the median LVOT flow velocity.Results: Feasibility of EOAPISA was 95% in the 114 patients. While there was a strong correlation between EOACont and EOAPISA, EOACont was greater than EOAPISA especially in patients with high LVOT velocity. In TOE cohort, both EOACont and EOAPISA similarly correlated with GOA. However, a fixed bias, which is supposed to exist in AS, was observed only between EOAPISA and GOA with smaller EOAPISA than GOA. The difference between EOACont and GOA was significantly greater with a larger EOACont relative to GOA in patients with high LVOT velocity than in those without (0.16±0.25 vs -0.07±0.10 cm2, P<0.001). In contrast, the difference between EOAPISA and GOA was consistent in both groups (-0.07±0.12 vs -0.07±0.15 cm2, P = 0.936). Conclusion: The PISA method was applied to estimate EOA of AS. EOAPISA could be an alternative parameter for AS severity grading in patients with high LVOT velocity in whom EOACont would overestimate the orifice area.

Impact of effective regurgitant orifice area on outcome of secondary mitral regurgitation transcatheter repair

Objectives To assess the value of effective regurgitant orifice (ERO) in predicting outcome after edge-to-edge transcatheter mitral valve repair (TMVR) for secondary mitral regurgitation (SMR) and identify the optimal cut-off for patients’ selection. Methods Using the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry, that included patients undergoing edge-to-edge TMVR for SMR between November 2008 and January 2019 in 8 experienced European centres, we assessed the optimal ERO threshold associated with mortality in SMR patients undergoing TMVR, and compared characteristics and outcomes of patients according to baseline ERO. Results Among 1062 patients with severe SMR and ERO quantification by proximal isovelocity surface area method in the registry, ERO was < 0.3 cm2 in 575 patients (54.1%), who were more symptomatic at baseline (NYHA class ≥ III: 91.4% vs. 86.9%, for ERO < vs. ≥ 0.3 cm2; P = 0.004). There was no difference in all-cause mortality at 2-year follow-up according to baseline ERO (28.3% vs. 30.0% for ERO < vs. ≥ 0.3 cm2, P = 0.585). Both patient groups demonstrated significant improvement of at least one NYHA class (61.7% and 73.8%, P = 0.002), resulting in a prevalence of NYHA class ≤ II at 1-year follow-up of 60.0% and 67.4% for ERO < vs. ≥ 0.3 cm2, respectively (P = 0.05). Conclusion All-cause mortality at 2 years after TMVR does not differ if baseline ERO is < or ≥ 0.3 cm2, and both groups exhibit relevant clinical improvements. Accordingly, TMVR should not be withheld from patients with ERO < 0.3 cm2 who remain symptomatic despite optimal medical treatment, if TMVR appropriateness was determined by experienced teams in dedicated valve centres.