Volume Overload In Mitral Regurgitation Research Articles

Eccentric remodeling in patients undergoing mitral valve repair due to severe degenerative mitral regurgitation: impact of relative wall thickness on clinical outcomes

Abstract Background Left ventricular (LV) volume overload in mitral regurgitation (MR) leads to a progressive increase in LV mass. Eccentric hypertrophy is defined as the relative wall thickness (RWT) <0.43, and LV hypertrophy is a frequently observed LV remodeling phenotype in patients with severe MR. However, the prognostic impacts of RWT in these patient groups are not well known. We tested the relationship between RWT and clinical outcomes in severe MR patients undergoing MV repair (MVR). Methods A total of 979 consecutive adult patients with severe degenerative MR and eccentric hypertrophy (55 ± 13 years, 616 males) who underwent MVR were retrospectively analyzed. The study population was stratified by the median RWT value (RWT=0.34) on baseline echocardiography [the lesser RWT group (RWT< 0.34 (n=651)) and the greater RWT group (RWT ≥0.34 (n = 328)). Results The patients in the lesser RWT group were younger (54±13 vs. 57±13, p<0.001) and had a significantly higher prevalence of hypertension and diabetic mellitus than those in the greater RWT group. The greater RWT group had significantly lower indexed LV systolic dimension, thicker ventricular walls, and higher LV ejection fraction as compared with those in the lesser RWT group. In Kaplan-Meier analysis, the greater RWT group had a significantly higher incidence of all-cause death (6.4% vs. 2.3%; log-rank p<0.001) and cardiac death (3.0% vs. 0.9%; log-rank p = 0.01) at five years after MVR than in the low RWT group. RWT≥0.34 was independently associated with higher all-cause and cardiac mortality in the multivariate Cox regression analysis. In subgroup analysis, RWT≥0.34 was associated with worse outcomes in men (P <0.001) but not in women (P = 0.23). Moreover, hypertensive patients in the greater RWT group showed the worst outcomes as compared with the three other groups. Conclusions We concluded that excessive ventricular hypertrophy, manifested as an increased relative wall thickness, is associated with a significantly increased risk of postoperative mortalities after mitral valve repair in patients with severe degenerative MR and eccentric hypertrophy. We also found that eccentric remodeling patterns and clinical outcomes differ according to sex and the presence of hypertension.

Dynamics of contractile function of the left atrium in patients, suffering ischemic mitral regurgitation

Objective. Estimation of mechanical function of the left atrium in patients, suffering an ischemic mitral regurgitation, using technology of the vector analysis of the endocardium movement speed. Materials and methods. Into prospective cohort of non-randomized investigation 107 patients ageing (56 ± 7.5) yrs old, 96 (89.7%) of them are men, were included. There were following criteria of selection: the Degrees I-III of ischemic mitral regurgitation by echocardiographic data, angiographically revealed an ischemic heart disease, demanding surgical revascularization, the sinus rhythm with the heart rate frequency from 60 to 89 in 1 minute, the improved echocardiographic visualization of the left atrium endocardium. Results. The indices of mechanical function of the left atrium are lowering in proportion to degree of severity of the ischemic mitral regurgitation. Longitudinal deformity and speed of the left atrium deformity reflects connection with the ischemic mitral regurgitation more, than conventional indices, applied for estimation of the left atrium geometry. The data obtained witnesses thet comparable ultrastructural changes in atrium, occurring in chronic volume overload of mitral regurgitation from Degree II and higher. The changes and velocity of the atriums deformity may be associated with severity of regurgitation. Conclusion. Significance of the left atrium mechanical function is associated with the ischemic mitral regurgitation and depends on mechanical remodeling of the left atrium. Studying of dynamics of the left atrium mechanical function in patients with mitral regurgitation may appear perspective and beneficial while doing estimation of its hemodynamical significance and choice of surgical approach as additional intervention on a mitral valve.

Reverse remodeling of left heart following mitral valve repair in case of mesenchimal dysplasia

Objectives. Volume overload in mitral regurgitation leads to compensatory dilation of the left heart chambers. Surgical correction promotes reverse remodeling of the heart. In this study, focus was placed on the changes in the left heart resulted from mitral regurgitation correction by using two different surgical techniques for mitral valve repair. Methods. 94 patients with posterior mitral valve prolapse were randomized in two groups. The first group patients underwent artificial chordal replacement, while a leaflet resection technique was used for the patients of the second group. Preoperative transthoracic and intraoperative transesophageal echocardiography was performed for all patients and data were obtained at 10-12 days after surgery and during long-term follow up. Results. In the early postoperative period, significant reverse remodeling of the left heart chambers was observed (LA 5.4-4.6, p <0.05; LVEDD 5.8-4.9 p <0.05; LVESD 3.6 - 3.1 p <0.05) - LA 5.2 - 4.5 p <0.05; LVEDD 5.8 - 4.8 p <0.05; LVESD 3.5 - 3.2 p <0.05. The mitral valve orifice area in the groups was 3.3 - 3.3 - 3.2 when replacing chords and 3.5 - 3.4 - 3.2 when doing resection, with p being equal to 0.32, 0.36 and 0.51 respectively. The mean diastolic gradient in the first group was 2.0 - 3.0 - 3.0 mm Hg, while in the second one it amounted to 2.3 - 3.2 - 3.3 mmHg, with p <0.05. Conclusion. The authors conclude that significant remodeling of the left heart occurs in the early postoperative period. In the immediate postoperative period, the mitral valve area tends to decrease and the gradient has a tendency to increase in both groups, with no significant changes observed in the late postoperative period.

Quantification of left ventricular interstitial fibrosis in asymptomatic chronic primary degenerative mitral regurgitation.

The optimum timing of surgery in asymptomatic patients with chronic severe primary degenerative mitral regurgitation (MR) remains controversial, and further markers are needed to improve decision-making. There are limited data that wall stress is increased in MR and may result in ventricular fibrosis. We investigated the hypothesis that chronic volume overload in MR is a stimulus for myocardial fibrosis using T1-mapping cardiac MRI. A cross-sectional study of 35 patients (age 60 ± 14 years) with asymptomatic moderate and severe primary degenerative MR (mean effective regurgitant orifice area, 0.45 ± 0.25 cm)(2) with no class I indication for surgery were compared with age and sex controls. Subjects were studied with cardiopulmonary exercise testing, echocardiography, and cardiac MRI. Longitudinal and circumferential myocardial deformation was reduced with MR when left ventricular ejection fraction (67% ± 10%) and N-terminal pro B Natriuretic peptide (126 [76-428] ng/L) were within the normal range. Myocardial extracellular volume was increased (0.32 ± 0.07 versus 0.25 ± 0.02, P<0.01) and was associated with increased left ventricular end-systolic volume index (r=0.62, P<0.01), left atrial volume index (r=0.41, P<0.05) but lower left ventricular ejection fraction (r=-0.60, P<0.01), longitudinal function (mitral annular plane systolic excursion, r=-0.46, P<0.01), and peak VO2 max (r=-0.51, P<0.05). In a multivariable regression model, left ventricular end-systolic volume index and left atrial volume index were independent predictors of extracellular volume (r(2)=0.42, P<0.01). Patients with asymptomatic MR demonstrate a spectrum of myocardial fibrosis associated with reduced myocardial deformation and reduced exercise capacity. Future work is warranted to investigate whether left ventricle fibrosis affects clinical outcomes.

Increased ACE and chymase-like activity in cardiac tissue of dogs with chronic mitral regurgitation.

The current study was designed to test the hypothesis that intracardiac angiotensin-converting enzyme (ACE) activity, chymase-like activity, and angiotensin (ANG) peptide levels are increased and are positively related to wall stress estimates in response to the chronic low pressure volume overload of mitral regurgitation produced by percutaneous chordal rupture in the dog. Chronic mitral regurgitation (MR) resulted in an increase in left ventricular (LV) end-diastolic volume [59 +/- 11 (SD) to 103 +/- 32 ml, P < 0.001], LV mass (96 +/- 17 to 114 +/- 23 g, P < 0.001), and a decrease in the LV mass-to-end-diastolic volume ratio (1.64 +/- 0.22 to 1.16 +/- 0.23 g/ml, P < 0.001) measured by magnetic resonance imaging. In vitro studies of heart tissue extracts demonstrated that the majority of ANG II-forming activity was from chymase-like activity rather than from ACE activity in five normal (83.5 +/- 7.5 vs. 6.04 +/- 5.2%) and seven MR hearts (86 +/- 3.9 vs. 2.6 +/- 1.7%). ACE activity (1.22 +/- 0.22 vs. 3.55 +/- 0.62 mU/g, P < 0.05) and chymase-like activity (9.42 +/- 4.64 vs. 20.60 +/- 8.41 nmol.g-1.min-1, P < 0.05) were increased in MR compared with normal hearts. ACE activity correlated with the LV mass-to-volume ratio (r = -0.93, P < 0.001) and LV diastolic wall stress ( r = 0.71, P < 0.05); however, chymase-like activity did not correlate with any hemodynamic parameter. ANG II levels were significantly higher in the midwall of the left ventricle in MR hearts than in normal controls (85 +/- 39 vs. 27 +/- 16 pg/g, P < 0.01). Our results demonstrate a positive correlation between LV diastolic wall stress and increased ACE activity with increased ANG II stores, suggesting that mechanical wall stress activated intracardiac ACE. Although chymase accounted for most ANG II formation in vitro in extracts of both normal and MR dog hearts, the significance of this enzyme in vivo remains unclear.

Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload.

It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload.

Early diastolic filling dynamics during experimental mitral regurgitation in the conscious dog.

Diastolic flow into the left ventricle during mitral regurgitation must increase as total stroke volume increases in response to the volume overload. The mechanisms that allow augmented diastolic filling are not fully defined. Accordingly, the left ventricle of five dogs was instrumented with a micromanometer and sonomicrometers and studied during the conscious state before (control) and after the creation of significant mitral regurgitation. Serial measurements were made at control and up to 4 weeks after the creation of the volume overload. Heart rate, peak systolic wall stress, and peak positive dP/dt showed no significant changes between control and subsequent observations. End-diastolic volume and total stroke volume progressively and significantly increased during the 4-week course. When compared with the control state (51 +/- 4, mean +/- SD), the filling fraction during the first 40% of diastolic time was increased at 4 days (67 +/- 10%, p less than 0.001), 2 weeks (72 +/- 6%, p less than 0.001), and 4 weeks (76 +/- 10%, p less than 0.001). During the period of adaptation to the volume overload, filling fraction correlated with end-diastolic volume (r = 0.52, p less than 0.02) and total stroke volume (r = 0.80, p less than 0.001). Compared with the control state (0.81 +/- 0.04), eccentricity of the left ventricle at end systole decreased at 4 weeks (0.79 +/- 0.06, p less than 0.05); the absolute change in this ratio during the first 40% of diastolic time was significantly augmented at 2 weeks (0.09 +/- 0.02, p less than 0.05) and 4 weeks (0.11 +/- 0.04, p less than 0.005) compared with control (0.05 +/- 0.02). Ventricular elastance (pressure/volume) at end systole (minimum volume) was 1.70 +/- 0.50 mm Hg/ml at control, 1.09 +/- 0.46 at 4 days (p less than 0.05), 0.96 +/- 0.42 at 2 weeks (p less than 0.01), and 0.99 +/- 0.22 at 4 weeks (p less than 0.01). Moreover, the elastance change during the rapid-filling phase was significantly diminished after creation of mitral regurgitation. Thus, during the volume overload of mitral regurgitation, the left ventricle accommodates a higher percentage of its total stroke volume during early diastole; this adaptation can be correlated with augmented systolic shortening, and thereby with increased restorative forces or elastic recoil, and with reduced chamber elastance and eccentricity during the early part of diastole. Other potential mechanisms include altered systolic and relaxation loading, augmented elastic recoil of the left atrium, left atrium and left ventricular pressure gradient, accelerated myocardial inactivation, and increased adrenergic stimulation.

Left atrial volume overload in mitral regurgitation: A two dimensional echocardiographic study

Left atrial volume in patients with mitral valve disease was studied with two dimensional echocardiography. The left atrial dimension was derived by planimetry of the left atrial area and, assuming spherical geometry, left atrial volume was calculated. Patients with severe mitral regurgitation had marked systolic expansion of the left atrium with large phasic changes in left atrial cubic dimension. Conversely, patients with severe mitral stenosis had small changes in the cubic dimension in comparison with the large left atrial size. Left atrial volumetric changes were similar among patients with atrial fibrillation and normal sinus rhythm. Therefore, left atrial volume overload is an additional two dimensional echocardiographic diagnostic feature of severe mitral regurgitation.