The mechanism of decrease in dynamic mitral regurgitation during heart failure treatment: importance of reduction in the regurgitant orifice size.

Mechanism of dynamic regurgitant orifice area variation in functional mitral regurgitation: Physiologic insights from the proximal flow convergence technique

Functional mitral regurgitation in patients with ischemic or dilated ventricles has been related to competing factors: altered tension on the leaflets due to displacement of their papillary muscle and annular attachments, which restricts leaflet closure, versus global ventricular dysfunction with reduced transmitral pressure to close the leaflets. In vivo, however, geometric changes accompany dysfunction, making it difficult to study these factors independently. Functional mitral regurgitation also paradoxically decreases in midsystole, despite peak transmitral driving pressure, suggesting a change in the force balance acting to create a regurgitant orifice, with rising transmitral pressure counteracting forces that restrict leaflet closure. In vivo, this mechanism cannot be tested independently of annular contraction that could also reduce midsystolic regurgitation. An in vitro model was developed that allows independent variation of papillary muscle position, annular size, and transmitral pressure, with direct regurgitant flow rate measurement, to test the hypothesis that functional mitral regurgitation reflects an altered balance of forces acting on the leaflets. Hemodynamic and echocardiographic measurements of excised porcine valves were made under physiological pressures and flows. Apical and posterolateral papillary muscle displacement caused decreased leaflet mobility and apical leaflet tethering or tenting with regurgitation, as seen clinically. It reproduced the clinically observed midsystolic decrease in regurgitant flow and orifice area as transmitral pressure increased. Tethering delayed valve closure, increased the early systolic regurgitant volume before complete coaptation, and decreased the duration of coaptation. Annular dilatation increased regurgitation for any papillary muscle position, creating clinically important regurgitation; conversely, increased transmitral pressure decreased regurgitant orifice area for any geometric configuration. The clinically observed tented-leaflet configuration and dynamic regurgitant orifice area variation can be reproduced in vitro by altering the three-dimensional relationship of the annular and papillary muscle attachments of the valve so as to increase leaflet tension. Increased transmitral pressure acting to close the leaflets decreases the regurgitant orifice area. These results are consistent with a mechanism in which an altered balance of tethering versus coapting forces acting on the leaflets creates the regurgitant orifice.

In patients with mitral regurgitation (MR), assessment of the severity of valvular dysfunction is crucial. Recently, regurgitant orifice area has been proposed as the most useful indicator of the severity of MR. The purpose of our study was to determine whether planimetry of the anatomic regurgitant orifice (ARO) in patients with MR is feasible by cardiovascular magnetic resonance (CMR) and correlates with invasive catheterization and echocardiography effective regurgitant orifice [ECHO-ERO] by proximal isovelocity surface area. Planimetry of ARO was performed with a 1.5-T CMR scanner using a breath-hold balanced gradient echo sequence true fast imaging with steady state precession (TrueFISP). CMR planimetry of ARO was possible in 35 of 38 patients and was closely correlated with angiographic grading (r=0.84, P<0.0001). In patients with MR grade > or =III on catheterization, CMR-ARO (0.60+/-0.29 cm(2) versus 0.30+/-0.19 cm(2), P<0.0001) as well as ECHO-ERO (0.49+/-0.17 cm(2) versus 0.27+/-0.10 cm(2)) were significantly elevated in comparison with MR grade <III. Further, CMR-ARO was closely correlated to CMR regurgitant fraction and volume (r=0.90 and r=0.91, P<0.0001, respectively) and catheterization regurgitant fraction and volume (r=0.86 and 0.83, P<0.0001, respectively). The correlation between CMR-ARO and ECHO-ERO was 0.81 (P<0.0001) and CMR slightly overestimated ECHO-ERO by 0.06 cm(2) (P<0.05). As assessed by receiver operating characteristic analysis, CMR-ARO at a threshold of 0.40 cm(2) detected MR grade > or =III as defined by catheterization, with a sensitivity and specificity of 94% and 94%, respectively. CMR planimetry of the anatomic mitral regurgitant lesion in patients with MR is feasible and permits quantification of MR with good agreement with the accepted invasive and noninvasive methods. Direct measurement by CMR is a promising new method for the precise assessment of ARO area and the severity of MR.

Although Doppler color flow mapping is widely used to assess the severity of mitral regurgitation (MR), a simple, accurate, and quantitative marker of MR by color flow mapping remains elusive. We hypothesized that vena contracta width by color flow mapping would accurately predict the severity of MR. We studied 80 patients with MR. Vena contracta width was measured in multiple views with zoom mode and nonstandard angulation to optimize its visualization. Flow volumes across the left ventricular outflow tract and mitral annulus were calculated by pulsed-Doppler technique to determine regurgitant volume. Effective regurgitant orifice area was calculated by dividing the regurgitant volume by the continuous-wave Doppler velocity-time integral of the MR jet. The cause of MR was ischemia in 24, dilated cardiomyopathy in 34 mitral valve prolapse in 12, endocarditis in 2, rheumatic disease in 2, mitral annular calcification in 1, and uncertain in 5. Regurgitant volumes ranged from 2 to 191 mL. Regurgitant orifice area ranged from 0.01 to 1.47 cm2. Single-plane vena contracta width from the parasternal long-axis view correlated well with regurgitant volume (r = .85, SEE = 20 mL) and regurgitant orifice area (r = .86, SEE = 0.15 cm2). Biplane vena contracta width from apical views correlated well with regurgitant volume (r = .85, SEE = 19 mL) and regurgitant orifice area (r = .88, SEE = 0.14 cm2). A biplane vena contracta width > or = 0.5 cm was always associated with a regurgitant volume > 60 mL and a regurgitant orifice area > 0.4 cm2. A biplane vena contracta width < or = 0.3 cm predicted a regurgitant volume < 60 mL and a regurgitant orifice area < 0.4 cm2 in 24 of 29 patients. No other parameter, including jet area, left atrial size, pulmonary flow reversal, or semiquantitative MR grade, correlated significantly with regurgitant volume or regurgitant orifice area in a multivariate analysis. Our results demonstrate that careful color flow mapping of the vena contracta of the MR jet provides a simple quantitative assessment of MR that correlates well with quantitative Doppler techniques.

Direct Visualization of Regurgitant Orifice by CMR Reveals Differential Asymmetry According to Etiology of Mitral Regurgitation

Acute mitral regurgitation (MR) was produced in 12 dogs by closed chest partial valvulectomy and the relative contributions of MR pressure gradient (MRG), the time for regurgitant flow (VSI), and the MR orifice area (MRA) to mitral regurgitant volume (MRV) assessed. Aortic and left atrial pressures, biplane left ventricular (LV) angiography, forward flow and mitral regurgitant flow (MRF) were measured following MR induction and following augmentation of left ventricular end-diastolic volume (EDV), increased aortic resistance (angiotensin), and in the presence of increased ventricular contractility (calcium or epinephrine). Mitral regurgitation orifice area was determined by calculation and the diameters of the mitral anulus and subvalvular areas measured angiographically. Angiotensin and volume infusion induced a substantial increase in MRF which was largely dependent on an increase in MRA but not MRG, while augmentation of contractility decreased MRF accompanied by a decrease in MRA, relatively independent of MRG. Left ventricular size and shape are major determinants of MRA and resultant MRF in acute mitral regurgitation. These findings may help to explain the effects of such factors as ventricular loading and volume on the clinical course of mitral regurgitation in man.

Diagnostic Value of Color Flow Mapping and Doppler Echocardiography in the Quantification of Mitral Regurgitation in Patients with Mitral Valve Prolapse or Rheumatic Heart Disease

ImportanceTwo randomized clinical trials of transcatheter edge-to-edge mitral valve repair in patients with secondary mitral regurgitation (the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR] and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]) report clinical outcome disparities that are largely unexplained. This appraisal sought to provide insight and an explanation for the differences in clinical outcomes (survival and hospitalization rates) in the 2 clinical trials. The mean echocardiogram Doppler results (and derived volume parameters) from each of the 2 clinical trials were compared and examined relative to the clinical outcomes. Special emphasis was placed on the assessment of mitral regurgitation proportionality coefficients that were determined as the ratio of effective regurgitant orifice area (EROA) to end-diastolic volume and the ratio of mitral regurgitant volume to end-diastolic volume.ObservationsIn this analysis of the differences in the clinical outcomes of the MITRA-FR and COAPT clinical trials, the ratio of the EROA to the end-diastolic volume in the COAPT study was found to be twice that of the MITRA-FR study (0.002 cm-1 vs 0.001 cm-1, respectively). The finding of a larger proportional EROA in the COAPT study suggests more severe mitral regurgitation compared with the MITRA-FR study, thereby providing a potential explanation for the different outcomes in the 2 clinical trials. In contrast, the ratio of the mitral regurgitant volume to the end-diastolic volume in the COAPT study was similar to (but slightly lower than) that of the MITRA-FR study (0.15 vs 0.18, respectively), indicating that the proportional mitral regurgitant volume was comparable in the 2 clinical trials. This finding contradicts the conclusions of the EROA analysis.Conclusions and RelevanceThe results of proportionality analyses based on EROA differ from those based on a volume analysis. This disparity casts doubt on the notion that an EROA analysis alone can explain the different results of the 2 randomized clinical trials.

Sizing for Mitral Annuloplasty: Where Does Science Stop and Voodoo Begin?

Ischemic mitral regurgitation has been recently demonstrated to carry important prognostic information in patients with left ventricular dysfunction due to coronary artery disease. There is no information regarding the prognostic role of functional mitral regurgitation in patients with non ischemic dilated cardiomyopathy. Patients with stable heart failure due to non-ischemic dilated cardiomyopathy were prospectively enrolled. All patients underwent a comprehensive echocardiographic assessment. Left ventricular diastolic (LVD) , systolic (LVS) diameters, left atrial diameter (LAD), ejection fraction (EF) and restrictive mitral filling pattern (RMP) was measured. Mitral regurgitant volume (RV) was measured by means of proximal isovelocity surface area method. The end point of the study was death or hospitalization for worsening heart failure. 80 patients (mean age 61±9 years; 82% male) were enrolled. 10 patients reached the end point of the study. At univariate Cox analysis, the echocardiographic variables associated with outcome were: EF (HR 0.84 95% CI 0.75 0.94; p=0.002), RMP (HR 5.2 95% CI 1.4 19.7; p=0.01) and RV (HR 1.046 95% CI 1.02 1.07; p=0.0005), LVS/BSA (HR 1.2 95% CI 1.02 1.4; p=0.03). At multivariate analysis RV remained the only variables independently associated with outcome (p=0.04). Result did not change when LVS/BSA substituted EF in the model. Receiving operator characteristics analysis documented that the area under the curve for RV in identifying patients with adverse outcome was 0.84±0.06 (95% CI 0.74 0.91) and the best cut off value for RV was 28 ml (sensitivity 80% 95% CI 44 97 and specificity 87% 95% CI 77 94). Patients with RV&lt;28 had a survival rate of 95% after 6 years from the index echocardiogram compared with 22% in those with RV&gt; 28 (longrank 23; p&lt;0.0001). In patients with non-ischemic dilated cardiomyopathy, RV was a main predictor of death or hospitalization for worsening heart failure.

Ischaemic mitral regurgitation (MR) is a dynamic condition influenced by global and regional left ventricular remodelling as well as mitral valvular deformation. Exercise testing plays a substantial role in assessing the haemodynamic relevance of MR and is recommended by current guidelines. We aimed to assess the prevalence, haemodynamic consequences, and prognostic impact of dynamic MR using isometric handgrip exercise. Heart failure patients with ischaemic cardiomyopathy and at least mild MR who underwent handgrip echocardiography at the University Hospital Duesseldorf between January 2018 and September 2021 were enrolled. Patients were followed-up for 1year to assess a combined endpoint including all-cause mortality, heart failure hospitalization, mitral valve surgery/interventions, ventricular assist device implantation and heart transplantation. One hundred thirty-three patients with ischaemic cardiomyopathy were included (age 75±10years; 21% female; LVEF 35±9%). At rest, 70 patients (53%) presented with mild MR, 54 patients had moderate MR (41%), and 9 patients (7%) showed severe MR. Twenty-five patients (20%) with non-severe MR at rest, developed severe MR during handgrip exercise. Patients with dynamic MR had larger left atrial dimensions, increased wall motion score index and larger tenting area at rest. Multivariate analysis identified MR severity during exercise [HR 1.998 (1.367-2.938)] and exercise TAPSE [HR 0.913 (0.853-0.973)] as predictors of the combined endpoint. The haemodynamic changes provoked by isometric exercise unmasked dynamic severe MR in a significant number of patients with non-severe MR at rest. These data may have implications for therapeutic decision-making in symptomatic patients with non-severe MR at rest.

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