Myocardial Textural Alterations in Aortic Stenosis

Myocardial fibrosis is an early morphologic alteration in patients with AS; it is a major determinant of diastolic and systolic dysfunction and also of the progression toward congestive heart failure. Myocardial fibrosis is a pathologic entity of extracellular matrix remodeling; in this pathophysiologic model of LV pressure overload (AS), reactive fibrosis occurs. Cell loss, mainly by autophagy and oncosis, significantly contributes to the progression of LV systolic dysfunction. Di Bello et al. investigated this topic, also performing intraoperative septal biopsy, with the following main histopathologic findings: (1) the presence of abundant interstitial fibrosis (i.e., connective tissue surrounding isolated myocytes or small groups of them), (2) frequent myocyte size and shape variability and myofibrillar disarray, and (3) an absence of inflammatory infiltrative cells.

Although endomyocardial biopsy is the traditional method to quantify myocardial interstitial collagen content, imaging techniques may be also used as an additional marker for myocardial fibrosis. Many imaging modalities and techniques have been used to assess the presence and the turnover of myocardial fibrosis. This process is important to differentiate reactive fibrosis from reparative fibrotic scar and inducible ischemia secondary to coronary artery disease. Some indirect evidence of the presence of fibrosis should be quantitatively obtained by some noninvasive test on the basis of their validation against myocardial biopsy studies. The assessment of reactive fibrosis could be obtained by functional evaluation; in fact, myocardial fibrosis leads to a loss of contractile reserve and an abnormal myocardial stiffness that is proportional to the degree of extracellular matrix deposition. The imaging techniques may be divided into methods to visualize fibrosis (cardiac magnetic resonance [CMR] and IBS) and techniques to assess subtle subclinical LV systolic and diastolic dysfunction (CMR, IBS, and two-dimensional strain and strain rate) ( Table 1 ).

To understand the IBS technique more fully, some essential aspects of the biologic basis for ultrasonic tissue characterization are described below.

Ultrasonic Tissue Characterization (Integrated Backscatter): The Biologic Basis

The different structural components of myocardium can influence its acoustic properties in physiologic and pathologic conditions (Rayleigh scattering). Rayleigh scattering is an acoustic phenomenon generated by the interaction between ultrasound and objects (scatterers) of small size (i.e., myocytes, blood cells, etc.), whose dimensions are much less than the ultrasound wavelength. Rayleigh scattering increases with frequency raised to the fourth power and provides much of the diagnostic information from ultrasound. The intensity of the backscattered echoes is proportional to the total number of scatterers, which means that the echo amplitude is proportional to the square root of the total number of scatterers. Collagen is a primary determinant of both scattering and attenuation of myocardial tissue ; a linear relationship has been found between IBS and hydroxyproline content in autopsied human hearts, with fibrotic changes associated with remote myocardial infarction. Furthermore, a significant direct correlation has been found between collagen content determined at biopsy and the regional echo amplitude. Scattering geometry is another determinant of myocardial reflectivity; in fact, myocardial scattering intensity directly depends on myocyte size. The microstructural arrangement of myocardial cells, embedded in a collagen matrix, may provide a sufficient local acoustic impedance mismatch different from normal myocardium scattering. Ventricular muscle fiber orientation might influence myocardial acoustic properties. In fact, the insonification angle might greatly influence the attenuation magnitude and backscatter (backscatter is maximal when the echo beam is oriented perpendicularly to the muscle fibers).

Myocardial attenuation and scattering are both influenced by tissue water content and blood flow: an increase in water content (tissue edema) and, to a lesser degree, coronary blood flow reduction (myocardial ischemia) might influence myocardium acoustic properties. Some considerations must be made regarding the scattering dynamic aspect: as described by Wickline et al. , peak values of IBS occur at end-diastole and minimal values at end-systole. However, these cyclic changes in the echo amplitude are related, even if not linearly, to the intrinsic myocardial contractile performance.

Ultrasonic Tissue Characterization (Integrated Backscatter): The Biologic Basis

The different structural components of myocardium can influence its acoustic properties in physiologic and pathologic conditions (Rayleigh scattering). Rayleigh scattering is an acoustic phenomenon generated by the interaction between ultrasound and objects (scatterers) of small size (i.e., myocytes, blood cells, etc.), whose dimensions are much less than the ultrasound wavelength. Rayleigh scattering increases with frequency raised to the fourth power and provides much of the diagnostic information from ultrasound. The intensity of the backscattered echoes is proportional to the total number of scatterers, which means that the echo amplitude is proportional to the square root of the total number of scatterers. Collagen is a primary determinant of both scattering and attenuation of myocardial tissue ; a linear relationship has been found between IBS and hydroxyproline content in autopsied human hearts, with fibrotic changes associated with remote myocardial infarction. Furthermore, a significant direct correlation has been found between collagen content determined at biopsy and the regional echo amplitude. Scattering geometry is another determinant of myocardial reflectivity; in fact, myocardial scattering intensity directly depends on myocyte size. The microstructural arrangement of myocardial cells, embedded in a collagen matrix, may provide a sufficient local acoustic impedance mismatch different from normal myocardium scattering. Ventricular muscle fiber orientation might influence myocardial acoustic properties. In fact, the insonification angle might greatly influence the attenuation magnitude and backscatter (backscatter is maximal when the echo beam is oriented perpendicularly to the muscle fibers).

Myocardial attenuation and scattering are both influenced by tissue water content and blood flow: an increase in water content (tissue edema) and, to a lesser degree, coronary blood flow reduction (myocardial ischemia) might influence myocardium acoustic properties. Some considerations must be made regarding the scattering dynamic aspect: as described by Wickline et al. , peak values of IBS occur at end-diastole and minimal values at end-systole. However, these cyclic changes in the echo amplitude are related, even if not linearly, to the intrinsic myocardial contractile performance.