| Chronic pressure overload of left ventricle (LV) is one of the most common causes of heart failure, and is commonly seen in hypertensive heart disease and aortic stenosis. As an adaption to increased afterload, the LV geometry will remodel, usually in the form of concentric myocardial hypertrophy. The hypertrophied myocardium is a compensatory mechanism for the increased afterload, and contribute to maintaining normal left ventricular ejection fraction (LVEF). As the disease proceed, the compensatory mechanism of myocardial hypertrophy finally fails. The LV filling pressure gradually increases and the LV cavity will eventually enlarge, called eccentric myocardial hypertrophy, and the LV function is proceeding to systolic heart failure. During chronic pressure overload, diastolic dysfunction is more apparent, and systolic dysfunction is frequently ignored because LVEF can be preserved for a long time.Previous studies indicated that LV systolic function was impaired in LV remodeling patients with normal LVEF. Rosen et al reported that LV concentric remodeling was related to regional systolic dysfunction in patients of coronary atherosclerosis. Imbalzano et al reported decreased systolic function in hypertensive patients with LV concentric remodeling, especially for longitudinal systolic function which was impaired even before myocardial hypertrophy occurred. Myocardial dysfunction during chronic pressure overload is closely related to pathological changes within myocardium. Affected by pressure overload, more collagen deposited in the extracellular matrix, resulting in myocardial interstitial fibrosis. Regional myocardial fiber disarray can also occur as a result of long-time pressure overload. Interstitial fibrosis and myocardial fiber disarray may change the normal LV geometry, disturbing myocardial systolic mechanism and cardiac conduction system, and may lead to progressive heart failure, ventricular arrhythmia and sudden cardiac death. Due to the complex LV myocardial structure and the uneven distribution of pathologic changes between subendocardial, middle, and subepicardial layers, the influence of fibrosis and disarray on LV systolic function is very complicated.Interstitial fibrosis and myocardial fiber disarray are independently related to prognosis. Previous researchers identified a correlation between interstitial fibrosis and LV systolic and diastolic function, as well as adverse cardiac events such as fatal arrhythmia and heart failure. Varnara et al reported that, in hypertrophic cardiomyopathy, young patients who died suddenly seem to have severe disarray, whereas interstitial fibrosis was the basis of heart failure, as well as a risk factor for ventricular arrhythmia in older patients.Myocardial interstitial fibrosis can be visualized by SPECT-molecular labeling, PET-perfusable tissue index and cardiac magnetic resonance imaging (MRI) delayed enhancement. As nuclear imaging, SPECT and PET imaging are radioactive and are not widely available. MRI is limited by expensive cost and long examination time. Additionally, MRI delayed enhancement could not detect diffuse interstitial fibrosis. Currently there are few techniques for myocardial fiber organization analysis. Myocardial fiber disarray can be assessed by diffuse MRI imaging, however, this technique is limited by high cost, complicated operations and is hardly available.Speckle tracking echocardiography (STE) has the ability of accurate evaluation of global and regional LV function. STE is sensitive to subclinical systolic dysfunction, which is often difficult to detect with traditional echocardiography. Moreover, STE is noninvasive, non-radioactive and has great reproducibility. Normal strains including longitudinal, circumferential and radial strains can be calculated using speckle tracking analysis, and can reflect myocardial function to some extent. However, the movement of regional myocardial is a three-dimensional vector with certain magnitude and direction during the cardiac cycle. As the component vectors of main strain vector on longitudinal, circumferential and radial coordinate axes, normal strain vectors could not reflect the magnitude and direction of myocardial three-dimensional vector. Main strain vector may provide additional information to more comprehensive evaluation of myocardial systolic function and mechanism.This study aimed to reveal the serial changes of LV systolic function during chronic pressure overload using STE, and for the first time, to calculate the magnitude and direction of main strain vector to evaluate myocardial systolic mechanism more comprehensively during pressure overload. Moreover, this study explored the relation of regional myocardial function to interstitial fibrosis and myocardial fiber disarray.This study included two parts as follows:Part1Serial Changes of Left Ventricular Systolic Function During Adaption to Chronic Pressure Overload:an Echocardiographic Study.Objective The aim of this part was to assess the serial changes of LV systolic function during adaption to chronic pressure overload.Methods Eleven Beagle canines aged8-12weeks were enrolled, which were randomized into the aortic constriction (AC) group (n=6) and the Sham group (n=5). The AC group underwent open chest surgery and had the ascending aorta constricted. The Sham group underwent only open chest surgery, without their ascending aorta being constricted. Two-dimensional echocardiographic data were acquired at baseline and at1,3, and6months after ascending aorta constriction. LV wall thickness and LV diameter were measured on two-dimensional images, and cross-sectional area (CSA) was calculated. LV volumes and LVEF were measured by bi-plane Simpson’s method. Diastolic mitral flow peak velocities (E, A) were measured with pulse wave Doppler. Diastolic velocities of Mitral annulus (e’, a’) were measured with tissue Doppler imaging. Regional longitudinal strain (SL), circumferential strain (SC) and radial strain (SR) were evaluated by speckle tracking analysis. The value of systolic main strain vectors including longitudinal-circumferential main strain vector (ELc), longitudinal-radial main strain vector (ELR) and circumferential-radial main strain vector (ECR) were calculated, as well as the angle of each main strain vector (θLC,θLr, θCR).Results①At3months after ascending aorta constriction, LV wall thickness and CSA in the AC group were significantly greater than those in the Sham group (p<0.05).②At1month after ascending aorta constriction, early diastolic velocity of mitral annulus (e’) were significantly decreased in the AC group when compared with the Sham group (p<0.05).③LVEF showed no significant difference between the two groups throughout the study.④Compared to the Sham group, SL were initially impaired at an early stage, followed by the decrease of SR at a later period in the AC group (p<0.05); SC showed no difference or slightly elevated in the AC group.⑤ELC showed no difference between the two groups at1month and3months after the operations, and was significantly decreased at6month in the AC group (p<0.05); ELR was decreased since3months after the operations, and ECR was impaired at6months in the AC group (p<0.05). Compared to the Sham group,θLC and θCR began to decrease since1month and3months, respectively, in the AC group; θLR was initially decreased at1month, then gradually increased and was greater than that of the Sham group at6months (p<0.05).Conclusion During the adaption to chronic pressure overload, LV systolic strains changed prior to LVEF changes. Impairment of SL occurs at an early stage, followed by the decrease of SR later. SC could maintain in the normal range or slightly elevated to compensate for normal LVEF. As adaption to pressure overload, SL was decreased initially, simultaneously SR and SC were normal or greater, as reflected by the preserved magnitude but more circumferential direction of main strain vector. Speckle tracking echocardiography has high sensitivity in detecting early impairment of myocardial dysfunction. Systolic main strain vectors provide more comprehensive evaluation of myocardial systolic function and mechanism. Part2Relationship of Regional Myocardial Systolic Function with Myocardial Fibrosis and Myocardial Fiber Disarray:a Two-dimensional Speckle Tracking Echocardiographic StudyObjective The aim of this part was to study the relationship of regional myocardial systolic function with pathological changes including myocardial interstitial fibrosis and myocardial fiber disarray.Methods Eleven Beagle canines aged8-12weeks were enrolled, which were randomized into the aortic constriction (AC) group (n=6) and the Sham group (n=5). The AC group underwent open chest surgery and had the ascending aorta constricted. The Sham group underwent only open chest surgery, without their ascending aorta being constricted. Two-dimensional echocardiographic data were acquired at6months after ascending aorta constriction. Longitudinal strain (SL), circumferential strain (SC) and radial strain (SR) were evaluated using speckle tracking echocardiography. After echocardiographic examinations, the animals were sacrificed. The heart tissue was sectioned, then the sections were prepared and stained with Masson trichrome. Each section was examined, and the size of fibrosis was calculated and expressed as the percentage of interstitial fibrosis area relative to the total myocardial area (Fibrosis Area, FA), while the size of disarray was calculated and expressed as the percentage of myocardial fiber disarray area relative to the total myocardial area (Disarray Area, DA). The correlation of each systolic strain with FA and DA were analyzed.Results①SL and SR were significantly decreased in the AC group when compared with the Sham group (p<0.01), while SC showed no difference between the two groups.②FA, DA in the AC group were significantly greater than those in the Sham group (p<0.05).③SL and SC were significantly correlated to FA (r=0.662,p<0.001; r=-0.456. p=0.008, respectively).④SL and SC were significantly correlated to DA (r=0.619,p<0.001; r=-0.456, p=0.008, respectively).Conclusion Myocardial interstitial fibrosis and myocardial fiber disarray could result in impairment of SL and SR. Myocardial interstitial fibrosis area is associated with SL and SR. myocardial fiber disarray area is also associated with SL and SR. Interstitial fibrosis and myocardial fiber disarray can be assessed with myocardial strains. |
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