Identifying Early Changes in Myocardial Microstructure in Hypertensive Heart Disease

Abstract

The transition from healthy myocardium to hypertensive heart disease is characterized by a series of poorly understood changes in myocardial tissue microstructure. Incremental alterations in the orientation and integrity of myocardial fibers can be assessed using advanced ultrasonic image analysis. We used a modified algorithm to investigate left ventricular myocardial microstructure based on analysis of the reflection intensity at the myocardial-pericardial interface on B-mode echocardiographic images. We evaluated the extent to which the novel algorithm can differentiate between normal myocardium and hypertensive heart disease in humans as well as in a mouse model of afterload resistance. The algorithm significantly differentiated between individuals with uncomplicated essential hypertension (N = 30) and healthy controls (N = 28), even after adjusting for age and sex (P = 0.025). There was a trend in higher relative wall thickness in hypertensive individuals compared to controls (P = 0.08), but no difference between groups in left ventricular mass (P = 0.98) or total wall thickness (P = 0.37). In mice, algorithm measurements (P = 0.026) compared with left ventricular mass (P = 0.053) more clearly differentiated between animal groups that underwent fixed aortic banding, temporary aortic banding, or sham procedure, on echocardiography at 7 weeks after surgery. Based on sonographic signal intensity analysis, a novel imaging algorithm provides an accessible, non-invasive measure that appears to differentiate normal left ventricular microstructure from myocardium exposed to chronic afterload stress. The algorithm may represent a particularly sensitive measure of the myocardial changes that occur early in the course of disease progression.

Ultrasonic Assessment of Myocardial Microstructure in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy

“…9,10 The image analysis method is applied to transthoracic echocardiographic images with the following parameters: B-mode imaging, parasternal long-axis view, end-diastolic frame, and adequate visualization of the mid-to-basal inferolateral endocardial, myocardial, and pericardial regions (Figure 1). The pericardial area directly adjacent to the mid-to-basal inferolateral myocardium (i.e.…”

“…The SIC, as a marker of myocardial microstructure, represents aggregate myocardial tissue changes following interaction of the ultrasound signal through maximum thickness of the myocardium, as previously described. 9,10 In this study, we applied the ImageJ algorithm to quantify the SIC measure on echocardiographic images for all study participants while blinded to the genotype and clinical status. Previous studies have demonstrated correlation coefficients for inter-reader and intra-reader reproducibility of SIC at 0.89 and 0.90, respectively.…”

“…Detectable variations in the resulting signal distribution can yield quantifiable differences between diseased versus healthy myocardium. 9,10 We and others have shown that ultrasound-based tissue analyses can reveal alterations in myocardial microstructure that correlate with the histologic presence of myocardial fibrosis (including both interstitial and dense replacement fibrosis) in the setting of a variety of myopathic disease processes, such as hypertensive heart disease, dilated cardiomyopathy, and post-infarct ischemic injury. 10–18 Therefore, in this pilot study, we evaluated how ultrasound-based analytical techniques compare to CMR for assessing myocardial tissue-level alterations in HCM.…”

“…9,10 We and others have shown that ultrasound-based tissue analyses can reveal alterations in myocardial microstructure that correlate with the histologic presence of myocardial fibrosis (including both interstitial and dense replacement fibrosis) in the setting of a variety of myopathic disease processes, such as hypertensive heart disease, dilated cardiomyopathy, and post-infarct ischemic injury. 10–18 Therefore, in this pilot study, we evaluated how ultrasound-based analytical techniques compare to CMR for assessing myocardial tissue-level alterations in HCM. We hypothesized that the echocardiographic signal intensity coefficient (SIC), an echocardiography-based measure of myocardial microstructure, can effectively detect tissue-level alterations in HCM sarcomere mutation carriers with and without LV hypertrophy.…”

Numeric reconstruction of 2D cellular actomyosin network from substrate displacement

“…Along with myosin, microfilaments are responsible for cellular contraction. The study of these filaments could be important because their organization may be related to pathological changes in myocardial tissue (Hiremath et al, 2014), as extracellular matrix (ECM) microstructure is related to alignment of cells and cytoskeleton morphology (Fernandez and Bausch, 2009;Rhee and Grinnell, 2007;Tomasek et al, 2002). Cells adhere to their substrate through integrins, transmembrane proteins which form focal adhesions.…”