Ultrasonic Backscatter and Serum Marker of Cardiac Fibrosis in Hypertensives

Abstract

Abstract-Elevations in the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP) Ͼ127 g/L have been found to predict severe myocardial fibrosis in hypertensive patients. This study was designed to assess whether ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the severity of myocardial fibrosis as estimated by serum PIP. Thirty-four subjects were included in the study. Serum PIP was measured by specific radio immunoanalysis. Backscatter cyclic variation and maximal intensity were measured in 6 regions throughout the left ventricle. The subjects were divided into 3 groups: 14 normotensives with PIP Ͻ127 g/L (group 1), 12 hypertensives with PIP Ͻ127 g/L (group 2), and 8 hypertensives with PIP Ͼ127 g/L (group 3). A n exaggerated accumulation of fibrillar collagens type I and type III occurs throughout the free wall and interventricular septum of animals 1,2 and humans 3,4 with primary arterial hypertension and left ventricular hypertrophy (LVH). A rise in collagen content has been shown to raise myocardial stiffness and promote abnormalities of cardiac function, electrical activity, and intramyocardial perfusion. 5 We have used serological markers of collagen turnover to address myocardial fibrosis of rats with spontaneous hypertension (SHR) 6 -8 and patients with essential hypertension 9 -12 and LVH. Serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type I synthesis, were higher in each setting of hypertensive heart disease, and there was a direct correlation between histological evidence and quantity of myocardial fibrosis and serum PIP concentration in SHR and hypertensive patients. Furthermore, in a recent study 12 we showed that hypertensives with serum concentrations of PIP Ͼ127 g/L have an almost 5-fold higher probability of presenting with histologically proven severe myocardial fibrosis than do hypertensives with serum PIP below this value. Thus, this cutoff value of PIP can be used to separate hypertensives likely presenting with severe myocardial fibrosis from subjects with nonsevere fibrosis. 13 Quantitative characterization of myocardial texture by analysis of ultrasonic reflectivity has been experimentally 14 -17 and clinically 18,19 shown to correlate with the collagen content of the myocardial tissue. We thus have hypothesized that PIP serum concentrations above 127 g/L should be associated with alterations in myocardial ultrasonic reflectivity detected by backscatter analysis. To test our hypothesis, maximal intensity (MI) and cyclic variation (CV) of backscatter signal were analyzed in normotensive subjects and hypertensive patients classified according to their serum concentrations of PIP. Methods SubjectsThe study population consisted of 34 subjects (27 men and 7 women, mean age 52 years, range 42 to 68 years) who were referred to our unit for routine cardiac evaluation. Twenty subjects presented elevated systolic blood pressure of Ͼ139 mm Hg and diastolic blood...

Long-Term Treatment with Valsartan Improved Cyclic Variation of the Myocardial Integral Backscatter Signal and Diastolic Dysfunction in Hypertensive Patients: The Echocardiographic Assessment

“…Most patients had mild to moderate LV hypertrophy with LV mass indexes ranging from 96 to 166 g/m 2 (10-90 percentile). Previous studies reported that the IBS-CV of the mid-septum in normo- tensive subjects was 6.5-7.0 dB (13,14), which was higher than the IBS-CV levels (5.08±0.51 dB) in our patients. Thus, it is suggested that myocardial collagen deposition was increased in patients in this study.…”

“…Among the tissue characterization parameters, the IBS-CV and the peak diastolic IBS value are commonly used as non-invasive parameters of myocardial fibrosis in hypertensive patients. However, the IBS-CV analysis has higher sensitivity than the peak diastolic IBS analysis (13,14,22). Thus, in the present study, the IBS-CV was used as a measure of myocardial fibrosis.…”

“…The integrated backscatter signal (IBS) is a non-invasive measure of the acoustic characterization of myocardial tissue. It has been shown that reduction in the cardiac cycle-dependent variation of the IBS (IBS-CV) reflects myocardial collagen deposition in hypertensive hearts (13,14). Thus, we performed a prospective multi-center trial to determine the effects of 12 months of treatment with valsartan on myocardial IBS-CV, LV hypertrophy, and LV function as assessed by echocardiography.…”

Myocardial Ultrasound Tissue Characterization in Patients with Chronic Renal Failure

“…At the same time, IBS CV was found to be significantly and inversely related to the percent fibrosis area as assessed by endomyocardial biopsy in patients with dilated cardiomyopathy (17) and to the myocardium/fibrosis ratio in patients with aortic stenosis (18). Furthermore, in patients with EH, a decreased CV of backscatter signal is associated with an increase in serum procollagen type I C-peptide, a specific circulating marker of cardiac collagen content (30). In our study, the modest reduction of IBS CV that was observed in patients with CRF and the more relevant decrease of CV IBS that was observed in patients with ESRD, as well as the significant correlation with indices of systolic function, might reflect a progressive impairment of LV contractile performance, possibly associated with an increase in myocardial collagen content.…”

Serum markers of angiogenesis and myocardial ultrasonic tissue characterization in patients with dilated cardiomyopathy

“…Ultrasonic tissue characterization with integrated backscatter (IB) offers a promising method for the assessment of myocardial texture and intrinsic contractile performance [7,8]. Previous studies have investigated ultrasonic tissue characterization in patients with DCM, and have shown that the analysis of IB has the potential to assess the myocardial interstitial fibrosis and intrinsic myocardial contractility in DCM [9,10].…”