Impact of mitral regurgitation on left ventricular anatomic and molecular remodeling and systolic function: implication for outcome

Abstract

The aim of the study was to assess the impact of mitral regurgitation (MR) on left ventricular (LV) anatomic and molecular remodeling and function and to determine whether early LV remodeling and function predict long-term outcome in experimental organic MR. A new rodent model of chronic MR was created. Twenty-eight rats had surgically induced MR, twelve rats had a sham operation, and twelve rats had no operation. LV diameters, volume, and mass and LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were assessed using echocardiography in the early stage of MR (6 and 12 wk after induction of MR). LV hemodynamics was assessed invasively. Cardiac alpha- and beta-myosin heavy chains and sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2) were measured to assess molecular remodeling and contractility. Cox's proportional hazard ratios (HR) were used to identify outcome predictors. Early LV dilation was demonstrated in rats with MR when LVEF and LVFS were still normal. LV remodeling was associated with an increase in LV end-diastolic pressure and decrease in maximal change in pressure over time. Shifting of alpha- to beta-myosin and reduced SERCA2 were observed in rats with MR. Cox's proportional hazard analysis showed that LV end-diastolic diameters (HR, 1.2-2.4; P = 0.007) and LV end-diastolic volume (HR, 1.1-1.4; P = 0.005) at 6 wk and LV mass index (HR, 1.1-2.0; P = 0.004) at 12 wk after induction of MR were significantly associated with 1-yr mortality. However, LVEF (HR, 0.7-6.8 for the 6 wk, P > 0.05; and HR, 0.4-3.2 for the 12 wk, P > 0.05) and LVFS (HR, 0.4-1.4 for the 6 wk; and 0.4-3.1 for the 12 wk, P > 0.05) did not predict late death. Chronic MR leads to LV anatomic and cellular remodeling and impaired contractility. The time course of LV remodeling and function changes in the rat model of MR is similar to humans. Prediction of outcome may be achieved by assessments of early LV remodeling.

Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

“…MR was induced using techniques which were previously described. 16 An intracardiac echocardiographic catheter (Acuson/Siemens Corporation, Mountain View, CA) was used to obtain transesophageal echocardiographic images to assess the severity of MR.…”

“…MR was induced using techniques which were previously described. 16 An intracardiac echocardiographic catheter (Acuson/Siemens Corporation, Mountain View, CA) was used to obtain transesophageal echocardiographic images to assess the severity of MR. 17 MR was considered significant if a regurgitant jet area occupied >40% of left atrial area with a visible MR vena contracta or a reversed pulmonary venous flow pattern.…”

“…40 In addition, MR is acutely and mechanically induced in all animal models of organic MR. [9][10][11]14,16,40 Progression of LV remodeling, therefore, may be different from patients with degenerative mitral valve disease in which the severity of MR often increases gradually unless rupture of the chordae tendineae of the mitral valve occurs. Although this study evaluated the effect of β-blockade in acute and chronic stages of organic MR by designating the early and late β-blockade groups, one should not overextrapolate experimental results to clinical patients.…”

Predictive value of ischemic mitral regurgitation during the acute phase of ST elevation myocardial infarction treated with primary coronary intervention for left ventricular remodeling in long-term follow-up

“…Results of other studies were conflicting, probably because of small number of patients collected and different reperfusion strategies [21]. Experimental studies showed direct influence of MR on remodeling and on extracellular matrix growth [22]. Amigoni et al [23] in 496 patients with left ventricular dysfunction during acute MI, demonstrated correlation between the grade of MR and end-diastolic or end-systolic left ventricular volumes, increased sphericity index and decreased LVEF at 1 year.…”

Experimental Impact of Mucopolysaccharidosis on Right Atrial Contractile Capacity of Skinned Fibers

“…Considering that patients with chronic MR may stay asymptomatic for a long time and regarding the reversibility of disease progress and contractile reserve after cardiac surgery we wanted to objectify this impact on 3 different groups of patients with different mitral valve disease [10].…”