DCM is one of the most common causes of heart failure. It is the most common primary myocardial disease and is characterized by ventricular dilation and myocardial dysfunction without hypertension, valvular disease, congenital heart disease or ischemic heart disease. The pathological basis involves extensive myocardial degeneration, atrophy and fibrosis, and myocardial interstitial fibrosis is the most common form. Its main characteristics are left ventricular enlargement, diffuse reduction in ventricular wall motion, and decreased systolic and diastolic functions. In patients with suspected heart failure or left ventricular dysfunction, echocardiography is the most important means to determine the diagnosis of dilated cardiomyopathy by assessing the presence and severity of left ventricular dilation and dysfunction. Some studies suggest that in the development of congestive heart failure in patients with DCM, with the complex geometric changes in the left ventricle, left ventricular structure and myocardial systolic and/or diastolic function also change. In the absence of abnormal load or coronary artery disease, the reduction in EF and left ventricular diastolic function can preliminarily diagnose DCM. In this study, LVEDD, LVEDS, LVMI, LVEDV, and LVESV were increased, and LVEF, FS, SV, CO, and CI were decreased in the DCM group, which can be used to evaluate the severity of left ventricular dilation and left ventricular systolic function decrease. LA, LAVI, average E/e′, and E/A increased, whereas septal e′ and lateral e′ decreased, suggesting that DCM patients had a certain degree of diastolic dysfunction with decreased left ventricular systolic function. It is believed that there is a disorder and degeneration of myocardial fibers in DCM. Collagen fiber hyperplasia and glycogen content reduction were observed in myocardial tissue, which caused patients to have extensive myocardial lesions, myocardial contractile weakness and significantly reduced left ventricular function, similar to the results of previous studies.
According to the arrangement of the cardiac muscle bundle, the left ventricle is composed of three myocardial fiber layers: superficial obliquely directed fibers, middle circumferentially directed fibers and a deep inner layer with longitudinal fibers. The three layers of myocardium account for 25%, 53–59%, and 20% of the ventricular wall thickness, respectively. The long axis of the subendocardial fibers is more or less at right angles to the long axis of the fibers forming the subepicardial layer. The endocardial and epicardial myocardial bundles originate from the base, surround the apex of the heart, and then return to the basal area to form a spiral structure. Longitudinal strain mainly reflects longitudinal myocardial fiber function under the endocardium, while circumferential strain mainly reflects annular myocardial fiber function in the middle layer . Studies have shown that longitudinal arrangement (up to 70%) is the most common type of left ventricular myocardial fiber. Longitudinal fibers have an important contribution to overall ventricular function. The longitudinal peak strain is significantly related to myocardial fibrosis [21, 22, 23], and the longitudinal function is closely related to hemodynamic changes rather than changes in short axis performance . However, the results of layered speckle tracking analysis showed that the LS and CS of the three layers in patients with DCM were significantly lower than those in the normal group, showing LSendo > LSmid > LSepi, CSendo > CSmid > CSepi, indicating that the overall left ventricular function was impaired, longitudinal and axial function were reduced, and the degree of myocardial injury in each layer and direction was different. Both LS and CS decrease layer by layer from the endocardium to the epicardium. The strain represents the deformation of myocardial fiber relative to the original size, whose production is not isolated but integral. The motion of the left ventricular wall depends on the synergistic effect between longitudinal and circumferential muscle bundles from all directions. DCM myocardium changes due to loss of cardiomyocytes, "slippage" of cardiomyocytes in the wall, interstitial fibrosis with residual cardiomyocyte hypertrophy, etc. The myocardial structure changes due to fiber disorder and/or an increase in the proportion of the longitudinal myocardial tract, which causes the left ventricular cavity in DCM patients to be enlarged, the left ventricular mass and volume to be increased, the myocardial rotation angle to be reduced, the longitudinal and circular motion and deformation ability of the three left ventricular layers to be decreased, and the peak strain to be decreased. Due to the difference in tension caused by the different ratio of curvature of the left ventricular endocardium and epicardium, the degree of subendocardial myocardial fibrosis in DCM patients is greater than that of the middle and subepicardial myocardium, which resulted in the decrease in LS and CS from endocardium to epicardium. Although the LS and CS of the three layers were significantly reduced, compared with the control group, the trend of layer-by-layer reduction from the epicardium to the endocardium was maintained. It is believed that the effect of myocardial fibrosis on the structural and functional changes in each layer of myocardium is balanced and diffuse.
Although DCM is considered a nonischemic myocardial disease, patients can also experience diffuse changes in MBF in the early stages of the disease. MBF injury is multifactorial, and regardless of the pathophysiology, damage to MBF in DCM may lead to myocardial ischemia and progressive deterioration of myocardial function. Most of our knowledge about the regulation of coronary circulation and the characteristics of coronary perfusion are based on measurements obtained from epicardial coronary artery and tissue perfusion measurements. However, the measurements obtained from the epicardial coronary artery may mask the true blood flow of myocardial vessels due to its main function.
The coronary artery system is composed of three parts with different functions: the proximal segment is represented by the epicardial coronary artery, which has the volume function; the middle segment is represented by the anterior artery, which has the function of maintaining the pressure at the beginning of the small artery within a narrow range; and the distal segment is represented by the intramural small artery, which has the function of matching myocardial blood supply and oxygen consumption. The latter two constitute the coronary microcirculation and are the main factors determining coronary blood flow. Among them, the distal small artery is the main part of MBF metabolic regulation, and 90% of the myocardial blood volume is located in the capillaries, which leads to a gradient increase in coronary perfusion in the myocardium and more subendocardial perfusion. Therefore, the research results show that A, β, and A × β in the two groups decreased layer by layer from the endocardium to the extracardiac region. Because of the specific and complex nonspecific histopathological features of DCM, its changes involve all myocardial components, including cardiomyocytes, interstitium, small blood vessels and endocardium, and are usually limited to the subendocardium. At the same time, patients with DCM in the end stage show spherical dilation, wall stress increases, and oxygen demand increases resulting in the myocardium undergoing recurrent ischemia. The corresponding increased metabolic demand cannot be met by increasing the blood vessel density, which further aggravates myocardial ischemia, decreased left ventricular function and abnormal MDF. The above changes are all significant in the subendocardial myocardium. Furthermore, the branches of the coronary artery in the epicardium often penetrate into the myocardial layer vertically and generate branches in the endocardial layer. To provide effective oxygen delivery, the ratio of capillary and myocardial fibers is 1:1. Most of the distal microarteries and capillaries pass through the length of myocardial cells; their direction is parallel to the direction of the myocardial fiber, and each capillary has a region responsible for its nutrition. The endocardium is the farthest layer of the extracorporeal coronary artery blood flow. During the process of contraction and relaxation, the pressure and blood flow of the endocardium will fluctuate violently. It is easy to observe structural and microvascular architecture changes in the early stage of the disease. Furthermore, many factors can easily influence in the early stage of the disease, which leads to earlier and more serious manifestations of myocardial ischemia in the subendocardial myocardium. Therefore, although the myocardial blood volume, blood flow velocity and blood flow of three layers of left ventricular myocardium in patients with DCM were all damaged, compared with the control group, the layer-by-layer decreasing trend from the epicardium to the endocardium was maintained. The changes in the myocardial microcirculation perfusion function in DCM patients were diffuse; however, due to the important role of the distal small artery of the coronary artery microcirculation and the degree of involvement of the three-layer myocardium in patients with DCM, the changes in the subendocardial myocardium were more serious in the three layers of the myocardium.
Correlation analysis results showed that only LSendo and Aendo had a relatively significant correlation. Domination of the left ventricular myocardium by longitudinally arranged myocardial fibers, in combination with the above research results, has led to speculation that it has an important contribution to the overall ventricular function, the degree of myocardial fibrosis, the regional myocardial blood volume, and MBF velocity and that MBF in DCM patients was more serious than that of the middle and subepicardial myocardium, which indicated that the longitudinal function of the left ventricular myocardium was closely related to the changes in myocardial microcirculation perfusion. Because the change in myocardial mechanics is a very complex process, the myocardial deformation of each layer depends on the active function of the layer and the passive motion of adjacent layers. The myocardial fiber layers are not isolated but interact with each other. The division of the myocardial layer itself is a kind of rough classification based on research and is not absolute, and it has a one-to-one correspondence with myocardial fibers. The limitations of the current analysis methods lead to myocardial changes in DCM patients from both mechanical and perfusion perspectives, but the correlation between them is weak.
4.1 Study limitations
Our study has several limitations: (1) the number of patients in the control group was relatively small; (2) patients with dilated cardiomyopathy in the study did not undergo myocardial biopsy and did not choose other examination methods that are more sensitive to myocardial deformation and perfusion as a reference; (3) there was no clear boundary between the three layers of left ventricular myocardium in the image, and the analysis software used in the study also failed to perform automatic stratification. The choice of the three-layer myocardium is manually selected by the researcher, which may affect the accuracy of the data. (4) Although MCE is a sensitive method for detecting coronary microcirculation disturbance and myocardial viability, its qualitative diagnosis mainly depends on the subjective interpretation of regional perfusion by experienced clinicians. There are few quantitative analysis studies on three-layer myocardial perfusion, and the sample size needs to be expanded for further research.