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

Abstract

Background Noninvasive assessment of altered myocardial tissue in patients with genetic mutations associated with hypertrophic cardiomyopathy (HCM) remains a challenge. In this pilot study, we evaluated whether a novel echocardiography-based assessment of myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations in HCM sarcomere mutation carriers with and without left ventricular hypertrophy (LVH). Methods and Results We studied 3 groups of genotyped individuals: sarcomere mutation carriers with LVH (clinical HCM; N=36), mutation carriers with normal LV wall thickness (subclinical HCM; N=28), and healthy controls (N=10). We compared measurements of echocardiographic SIC with validated assessments of cardiac microstructural alteration, including CMR measures of interstitial fibrosis (extracellular volume fraction, ECV), as well as serum biomarkers (NTproBNP, hs-cTnI, and PICP). In age-, sex-, and familial relation-adjusted analyses, the SIC was quantitatively different in subjects with overt HCM, subclinical HCM, and healthy controls (P<0.001). Compared to controls, the SIC was 61% higher in overt HCM and 47% higher in subclinical HCM (P<0.001 for both). The SIC was significantly correlated with ECV (r=0.72; P<0.01), with LV mass and E’ velocity (r=0.45, −0.60, respectively; P<0.01 for both), as well as with serum NT-proBNP levels (r=0.36; P<0.001). Conclusions Our findings suggest that the SIC could serve as a non-invasive quantitative tool for assessing altered myocardial tissue characteristics in patients with genetic mutations associated with HCM. Further studies are needed to determine whether the SIC could be used to identify subclinical changes in patients at risk for HCM and evaluating the effects of interventions.

Preclinical Alterations in Myocardial Microstructure in People with Metabolic Syndrome

“…It is important to note that ultrasonic signal intensity variation can be influenced by many factors, including collagen content and fibrosis, myocyte size, sarcomere length, as well as fiber orientation ( 30 ). While a previous study showed correlation of the SIC with myocardial fibrosis ascertained by cardiac magnetic resonance imaging ( 20 ), such data are not available in our sample. Thus, abnormalities observed in our study may reflect changes in myocardial architecture due to a number of different processes that remain unclear, including possible myocyte steatosis and fat infiltration.…”

“…In addition, alterations in microstructure were detected among patients with hypertrophic cardiomyopathy, as well as sarcomere gene mutation carriers in the absence of left ventricular hypetrophy. Importantly, the SIC was correlated with extracellular volume measures on cardiac magnetic resonance imaging, as well as other measures of LV diastolic function ( 20 ). We now extend these findings to cardiometabolic disease, and show that the SIC is abnormal in individuals with obesity and metabolic disease, even after accounting for hypertension.…”

“…In initial studies, we demonstrated abnormalities in myocardial signal intensity variation in hypertensive heart disease, which correlated with experimental models simulating pressure overload states ( 18 ). Further, a recently published study demonstrated alterations in ultrasonic signal intensity variation and cardiac microstructure in hypertrophic cardiomyopathy, as well as sarcomere-mutation carriers without left ventricular hypertrophy ( 20 ). In this study, ultrasonic signal intensity variation correlated with extracellular volume by cardiac magnetic resonance imaging, as well as left ventricular diastolic function parameters.…”

Ventricular diastolic dimension over maximal myocardial thickness is robust landmark of systolic impairment in patients with hypertrophic cardiomyopathy

“…Patients with HCM and preserved ejection fraction experience dyspnea, physiological activities limitation, angina-like chest pain, and experience inconspicuous risk of sudden cardiac death, which is diagnostically difficult to characterize using cardiovascular imaging [ 25 ]. The latter is among the most important reasons on necessity of novel studies that would yield innovative diagnostic parameters, with sufficient reproducibility and convenience of use in wide number of centers [ 26 , 27 ]. In the context of given arguments our preliminary findings are in part inspiring since tests for diagnostic potential of GFI reported on very high sensitivity and specificity of left ventricle diastolic dimension over maximal thickness of hypertrophied myocardium for recognizing systolic dysfunction [ 28 ].…”

Cardiac Microstructural Abnormalities Identify Women at Risk of Incident Heart Failure

“…12 Quantitative tissue analysis was performed as previously described. [4][5][6][7] Briefly, transthoracic B-mode parasternal long axis views were selected at end diastole. Images were inspected for quality and ability to visualize the mid-to-basal inferiolateral myocardial/pericardial interface.…”