Study On Intraventricular Pressure Gradient After Aortic Valve Replacement

It has recently been shown that although aortic valve replacement dramaticallyimproves the quality of life for patients with aortic stenosis by relieving the highpressure gradient and allowing the reversal of the left ventricle hypertrophic process(favorable remodeling). Severe complications such as stenosis or obstruction of theleft ventricle (LV) outflow tract and mitral valve insufficientia caused by antelocationdue to residual intraventricular pressure gradient are frequently confronted in thesepatients.Using accurate three diamensions (3-D) echocardiography and other methods,this study was designed to explore the mechanisms and correlation factors of residualintraventricular pressure gradient after valve replacement for aortic stenosis and theeffects of drug on cardiac remodeling regression. Our students have show a new wayand theoretical basis for further clinical therapy and recovery after aortic valvereplacement.Part 1 The clinical study on intraventricular pressure gradient after aortic valve replacementObjective: To investigate the mechanism and relation factors of left intra-ventricular dynamic gradients in patients with severe aortic valve stenosis aftervalve replacement.Methods: Fifty patients with severe aortic valve stenosis were included,Echo-Doppler study was performed one week after aortic valve replacement, and thepatients were divided into two groups (Ⅰ,Ⅱ). GroupⅠ, patients had systolic leftintra-ventricular velocities＞2.5m.s^-1. GroupⅡ, patients had velocities＜2.5m.s^-1. Theleft ventricular end-diastolic dimensions, the left ventricular end -systolic dimensions,the left ventricular outflow tract, the thickness of septum and posterior wall werecompared using SPSS program.Results: There was no operative mortality. The maximal left ventricularvelocities were increased significantly in 9 patients (more than 2.5m/s) and six ofthem had SAM syndrome. There were statistic significances (P＜0.05 and P＜0.01separately) excepting the posterior wall of left ventricular between the two groups.Conclusions: The systolic intra-cavitary gradients increased after aortic valvereplacement, which was related to the smaller left ventricular end-diastolicdimensions, the left ventricular end -systolic dimensions, the left ventricular outflowtract and the thickness of septum.Part 2 Effects ofβ-receptor blocker on intraventricular pressure gradient after aortic valve replacementObjective: To investigate the effects ofβ-receptor blocker on intraventricularpressure gradient and left ventricle remodeling after valve replacement for criticalaortic stenosis.Methods: This study assessed forty-two patients with peak systolic velocity＞1.8m/s who undergone aortic valve replacement surgery for critical aortic stenosis.Thirty-two patients who got a long term follow-up were randomly divided into twogroups: group (n=12), Metoprolol (6.25～25mg.kg^-1·d^-1); groupⅡ(n=20), control.The two groups were investigated about LV diastolic dimension, LV end systolic diameter, LV outflow tract diameter, thickness of interventricular septum and LVposterior wall, filament band velocity and pressure gradient of LV outflow tract, LVejection fraction (EF) and LV mass index (LVMI) for 6-76 months by Dopplerechocardiogram.Results: There was no death for all patients. Although all the LV diastolicdimension, LV end systolic diameter, LV outflow tract diameter were increasedcompared with early after aortic valve replacement, only the increase of LV outflowtract diameter in groupⅠshowed statistic difference (P＜0.05). In groupⅠthethickness of interventricular septum and LV posterior wall, filament band velocity andpressure gradient of LV outflow tract were significantly lower than early after aorticvalve replacement (P＜0.01). In groupⅡonly the decrease of filament band velocityand pressure gradient of LV outflow tract showed statistic difference (P＜0.05). TheEF in two groups indicated no significant difference. In groupⅠthe thickness ofinterventricular septum and LV posterior wall were significantly lower than groupⅡ(P＜0.05). The decrease of LVMI in two groups showed statistic difference and itwas lower in groupⅠthan in groupⅡ(P＜0.05).Conclusions:β-receptor blocker is a safe and reliable drug for those patientswho undergo aortic valve replacement surgery for critical aortic stenosis, which candecrease significantly the residual intraventricular pressure gradient and acceleratecardiac remodeling regression.Part 3 Effects of operation and drug on the extracellular matrix remodeling of cardiac hypertrophy in pressure overload ratsIn response to a variety of mechanical, hemodynamic, hormonal, and pathologicstimuli, the heart adapts to increased demands for cardiac work by increasing musclemass through the initiation of a hypertrophic response. Cardiac hypertrophy isobserved in various cardiovascular diseases such as hypertension, myocardialinfarction, valvular heart diseases, and hypertrophic cardiomyopathy. Clinical studies have demonstrated that cardiac hypertrophy is not only an adaptational state beforeheart failure but is an independent risk factor for ischemia, arrhythmia, and suddendeath. The accumulation of extracellular matrix (ECM) in the heart plays an importantrole in the development of cardiac hypertrophy. Myocyte hypertrophy and interstitialfibrosis in left ventricle (LV), refered to as remodeling, contribute to development ofdepressed cardiac performance. Accordingly, it is of critical importance to understandthe underlying mechanisms of cardiac hypertrophy and to develop therapeuticstrategies that will effectively inhibit the development and progression of LVremodeling.Cardiac extracellular matrix (ECM) consists of several groups of extracellularmacromolecules. As a major component, cardiac collagen provides alignment tomyocardial cells and serves as the skeleton of cardiac collagen network, Whichmaintains the ventricular chambers in normal structural architecture and function. Thematrix metalloproteinases (MMPs) are a family of structurally related endopeptidasesthat have the ability to degrade all components of the extracellular matrix, so they arethe major physiological regulators of the extracellular matrix.Objective: To investigate the role of collagen, metalloproteinase (MMP-1) andtissue inhibitor of metalloproteinase (TIMP-1) in cardiac hypertrophy andextracellular matrix remodeling and effect of operation and drug (Candesartan,Carvedilol) on cardiac hypertrophy due to pressure overload.Methods: Cardiac hypertrophy due to pressure overload was produced byabdominal aortic banding incompletely. Removing the abdominal aortic banding aftermodeling myocardial hypertrophy of rats and Candesartan or Carvedilol was givenorally for 4 weeks. Before the rats were killed, the change of hemodynamics wasmeasured. Then the pathobiological change of the hearts, the collagen expression andthe index of cardiac hypertrophy were measured. Eventually the mRNA and proteinexpressions of the MMP-1, TIMP-1 were tested by Real-time PCR and Western blotrespectively. Results: Abdominal aortic banding induced hypertrophy and extracellular matrixremodeling predominantly occurred on the left ventricular. The content of collagenand the expressions of MMP-1, TIMP-1 mRNA and protein were elevated (P＜0.01).After removing abdominal aortic banding and Candesartan or Carvedilol treatment,the index of cardiac hypertrophy and BP were degraded (P＜0.01), the total collagenand the expression of MMP-1 were decreased (P＜0.01).Conclusions: That increase of MMPs expression is responsible for thedestruction process of the ECM, and the TIMP-1 is responsible for the repair andremodeling process of the ECM, may play an important role in the cardiac ECMremodeling. Removing abdominal aortic banding and Candesartan or Carvediloltreatment may prevent the cardiac hypertrophy and extracellular matrix remodeling,which is associated with attenuation of increase of myocardial MMP-1.