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Analysis of transmural trends in myocardial integrated backscatter in patients with progressive systemic sclerosis
Analysis of Transmural Trends in Myocardial Integrated Backscatter in Patients With Progressive Systemic Sclerosis Keiji Hirooka, MD, Johji Naito, MD, Yukihiro Koretsune, MD, Hiroaki Irino, MD, Haruhiko Abe, MD, Minoru Ichikawa, MD, Yoshinori Yasuoka, MD, Hiroyoshi Yamamoto, MD, Katsuji Hashimoto, MD, Wakatomi Chin, MD, Hideo Kusuoka, MD, Michitoshi Inoue, MD, and Masatsugu Hori, MD, Osaka, Japan
Cardiac involvement in progressive systemic sclerosis (PSS) is common and has a strong negative impact on the prognosis, especially when autoantibodies are present. To determine whether ultrasonic tissue characterization can detect early ultrastructural changes in the sclerodermal myocardium, we analyzed the transmural heterogeneity in myocardial integrated backscatter (THIB). “A-THIB” was defined as the absolute difference in integrated backscatter between the left (subendocardial) and right (subepicardial) ventricular halves of the myocardium in the septum and posterior wall, and was measured in 11 patients with PSS and 10 age- and
Progressive systemic sclerosis (PSS) is a connective
tissue disease characterized by overproduction of collagen and its deposition in multiple organs, including the skin, lung, kidney, gastrointestinal tract, and heart.1 Myocardial fibrosis is the most common cardiac lesion in PSS, occurring in up to 50% of patients.2 Because cardiac involvement is one of the most frequent complications and strongly affects the overall prognosis, early detection and monitoring of myocardial involvement may decide therapeutic strategies. Myocardial integrated backscatter (IB) is a noninvasively determined parameter of the acoustic properties of myocardium and previously has been shown to reflect physiologic conditions, pathologic conditions, or both in the myocardium.3-9 Recent studies have suggested that the transmural trend in myocardial IB reflects the transmural heterogeneity From the Cardiovascular Divisions of Osaka National Hospital and Osaka Police Hospital (J.N.); and Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine (M.H.). Presented in part at the 13th Annual Scientific Sessions of the American Society of Echocardiography, June 2002, Orlando, Fla. Reprint requests: Keiji Hirooka, MD, PhD, Cardiovascular Division, Osaka National Hospital, 2-1-14, Hoenzaka, Chuo-ku, 5400006, Osaka, Japan (E-mail: [email protected]). Copyright 2003 by the American Society of Echocardiography. 0894-7317/2003/$30.00 ⫹ 0 doi:10.1016/S0894-7317(02)74427-1
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sex-matched healthy participants. A-THIB in patients with PSS was higher than that in healthy participants (1.3 ⴞ 1.3 vs 4.0 ⴞ 1.4 dB for the septum and 1.1 ⴞ 0.7 dB vs 2.8 ⴞ 0.4 dB for the posterior wall; mean ⴞ SD, respectively, P < .0005). Septal A-THIB was higher in patients with PSS with than without anti-Scl70 or antinucleolar antibodies (3.2 ⴞ 1.1 vs 5.0 ⴞ 1.0 dB, P ⴝ .0165). Early changes in the myocardium of patients with PSS, possibly related to increased interstitial collagen deposition, can be detected by quantitative analysis of THIB. (J Am Soc Echocardiogr 2003;16:340-6.)
of myocardial fibrosis and viability, in addition to quantifying the magnitude of cardiac cycle-dependent variation in IB.5,9 The purpose of this study was to clarify whether analysis of transmural heterogeneity in myocardial IB (THIB) can be used to detect early ultrastructural changes in the sclerodermal myocardium.
METHODS Patients The study population consisted of 11 patients who received a diagnosis of PSS on the basis of the criteria of the American Rheumatism Association.10 Patients with PSS were recruited from the collagen disease center of the Department of Dermatology at Osaka National Hospital. The mean duration of disease was 99.5 months (range, 24 to 240 months). Of this group, 7 patients had limited cutaneous type and 4 patients had diffuse cutaneous involvement. None of the patients had valvular heart disease, congenital heart disease, left ventricular (LV) hypertrophy, heart failure, or prior myocardial infarction, and none were taking cardioactive drugs. No electrocardiographic abnormalities were present at rest in any participant. Patients with respiratory failure, renal insufficiency, diabetes mellitus, or hypertension were excluded from the study. All patients in the study were clinically stable. As control participants, we evaluated 10 age- and
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sex-matched healthy volunteers who had no clinical, electrocardiographic, or radiographic evidence of heart disease. All patients had the serologic autoantibodies specific for PSS, anti-Scl70, antinucleolar, and anticentromere antibody, measured using standard techniques.10,11 All participants gave informed consent for participation in the study, which was approved by our institutional ethics committee. Conventional Echocardiography Before the IB study, all participants were examined using conventional 2-dimensional and M-mode echocardiography with Doppler analysis, to assess chamber size, wall thickness, wall motion, and the pulsed Doppler transmitral inflow velocities. Echocardiographic variables were measured in a standard manner by parasternal views.12 The pulsed Doppler transmitral inflow velocities were obtained from an apical 4-chamber view, and the Doppler sample volume was placed on the tips of the mitral leaflets to analyze the peak early diastolic LV filling velocity (peak E), the peak LV filling velocity during atrial contraction (peak A), the ratio of peak E to peak A (E/A), the deceleration time, and the isovolumic relaxation time. The Doppler recordings were made at a paper speed of 100 mm/s. The deceleration time was calculated by estimating the period from the peak early diastolic LV filling velocity to an extrapolation of the deceleration of flow to baseline. The “isovolumic relaxation time” was defined as the interval between closure of the aortic valve and the onset of the mitral flow. Ultrasonic Backscatter Instrumentation The IB imaging system consisted of a commercially available ultrasound system (SSD-2200; Aloka Co Ltd, Tokyo, Japan) with a 2.5-MHz frequency transducer. With this system, either conventional 2-dimensional and M-mode echo amplitude or the IB of myocardium using the power of tissue Doppler can be obtained. Unlike a conventional imaging system, however, the ultrasound signals are accessed with IB processor to produce a continuous signal that is proportional to the logarithm of IB in the power of tissue Doppler. The value of myocardial IB (IBc) is expressed as the power of the ultrasound backscattered from the myocardium in conventional imaging mode.5,7-9 IBc ⫽
冕
⫹⌬ ⫺⌬
兩m(t)兩2 dt
(1)
where m(t) is the signal received from the tissue (myocardium); is the position in time of the center of the region of interest (ROI); and ⌬ is the corresponding half-width in time. The value of myocardial IB (IBp) is obtained from the myocardium by measuring the power of the received radiofrequency signal. IBp ⫽
1 n
冘 n
k⫽1
关兵I' k共t兲其 2 ⫹ 兵Q' k共t兲其 2兴
(2)
where I ' (t) and Q' (t) are the real part and imaginary parts of the quadrature detector outputs, respectively; k represents the kth receipt for the same raster; and n is the packet size. IBp is calculated from the spatial integral of the signals, whereas IBc is the pure time integral. However, there is no essential difference between IBc and IBp because IB is obtained by measuring the average of signals in a ROI, and IBp is determined by measuring the average of signals over a period. The period is 4 ⫻ 1/4000 ⫽ 1 millisecond, because the pulse repetition frequency is 4 kHz and the packet size is 4 in this method. The variation in IB can be ignored within this period, therefore, IBp corresponds closely enough to IBc to assume equivalency. We carefully adjusted the time-gain controls in each patient to produce a uniform brightness of the myocardium without saturation. Data Analysis of Myocardial IB Subsequent to the conventional echocardiography, the IB study was performed by tracing the ROI along frozen M-mode images from the parasternal long-axis view. The ROI for backscatter measurements was traced midway between the endocardial and epicardial borders of the septum and posterior wall. We attempted to exclude the thick, bright lines of the endocardium and intramyocardial specular bright echoes from the ROI. The depth of the ROI was 5 mm in this study. After placing the ROI for backscatter measurements in the M-mode IB images, curves of myocardial IB were created. The magnitude of cyclic variation in IB (CVIB) was determined from these curves, as the difference between the minimum and maximum values. Because the monitor can display on 1 screen for 2500 seconds, we analyzed using the averaged values of 2 to 4 cardiac cycles according to the patient’s heart rate. Furthermore, this system calculates myocardial IB of both the distal and proximal halves in the ROI (the LV and right ventricular [RV] halves of the septum, and the epicardial and endocardial halves of the posterior wall) (Figure 1). We measured the THIB to evaluate the transmural trend of acoustic properties in myocardium. THIB measures the difference in IB (not the difference in the magnitude of CVIB) between the distal and proximal halves in the same ROI. Therefore, if the IB from subendocardial region of the posterior wall is much larger than the IB from the adjacent subepicardial region, then the THIB would be relatively large and positive. If, on the other hand, the IB from subendocardial region of the posterior wall is much smaller than the IB from the adjacent subepicardial region, then the THIB would be relatively large but negative. In this study, however, we evaluated the absolute value of the difference of the THIB (A-THIB) only to estimate the extent of the dispersion in THIB. With this system, A-THIB can be determined automatically in IB in the unit decibels (dB). It has been noted that this determination does not require calibration because the measurement in the same ROI along the same interrogating beam corrects for signal or attenuation loss
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Table 1 Comparison of demographics, clinical characteristics, and conventional echocardiographic parameters in healthy participants and patients with progressive systemic sclerosis Healthy Patients with participants PSS
Figure 1 Myocardial integrated backscatter (IB) image of septum of healthy participant (A) and of patient with progressive systemic sclerosis (PSS) (B) from parasternal long-axis view. M-mode myocardial IB image of left ventricle (LV) with trace of region of interest (ROI) (lower), global (upper), and regional (middle) curves of septal IB. Global and regional (upper vs lower half) magnitude of cyclic variation in IB were similar in healthy participants and patients with PSS, but transmural heterogeneity in myocardial IB was greater in patient with PSS (zoom-in view). Yellow line, Right ventricular half; green line, LV half; ECG, electrocardiogram.
resulting from transmission through tissue intervening between the transducer and the ROI.5 Data Reproducibility We determined intraobserver and interobserver variabilities in CVIB in 10 randomly selected records on the basis of observations by the same observer and by 2 independent observers, respectively. Absolute differences in global CVIB between observations were 0.6 ⫾ 0.7 dB (intraobserver) and 0.9 ⫾ 0.6 dB (interobserver) for the septum, and 0.8 ⫾ 0.7 dB (intraobserver) and 1.1 ⫾ 0.8 dB (interobserver) for the posterior wall.
No. of participants Age (y) Sex HR (bpm) LAD (mm) IVSth (mm) PWth (mm) LVDd (mm) LVDs (mm) FS (%) IVRT (ms) E (cm/s) A (cm/s) E/A DcT (ms) Autoantibodies Anti-Scl70 antibody Antinucleolar antibody Anticentromere antibody
10 54 ⫾ 15 9 F, 1 M 68 ⫾ 12 36.7 ⫾ 4.2 8.8 ⫾ 0.9 8.6 ⫾ 0.8 45.6 ⫾ 2.3 27.0 ⫾ 2.2 40.7 ⫾ 5.5 76.0 ⫾ 22.7 77.4 ⫾ 20.9 72.9 ⫾ 23.8 1.13 ⫾ 0.36 245 ⫾ 58
11 (7L, 4D) 52 ⫾ 8 10 F, 1 M 82 ⫾ 19 37.0 ⫾ 3.4 9.5 ⫾ 1.3 9.1 ⫾ 0.8 44.5 ⫾ 4.3 23.9 ⫾ 5.6 45.1 ⫾ 8.9 84.7 ⫾ 10.6 72.7 ⫾ 6.2 75.2 ⫾ 25.9 1.09 ⫾ 0.41 224 ⫾ 40
P value
P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS
4 (36%) 3 (27%) 2 (18%)
L, Limited cutaneous type; D, diffuse cutaneous type; F, female; M, male; HR, heart rate; LAD, left atrial diameter at end-systole; PSS, progressive systemic sclerosis; NS, not significant; IVSth, wall thickness of septum at end-diastole; PWth, wall thickness of posterior wall at end-diastole; LVDd, left ventricular diameter at end-diastole; LVDs, left ventricular diameter at end-systole; FS, fractional shortening; IVRT, isovolumic relaxation time; E, peak early diastolic left ventricular filling velocity; A, peak left ventricular filling velocity during atrial contraction; E/A, ratio of peak early diastolic filling velocity to peak filling velocity during atrial contraction; DcT, deceleration time. Values are expressed as mean ⫾ SD.
tyly were seen in all patients, whereas dysphagia was seen in 5 patients. Arthralgias were present in 6, arthritis in 1, calcinosis in 2, and telangiectasias in 7 patients. Two patients whose anticentromere antibodies were positive in limited cutaneous PSS were considered to have CREST syndrome. Conventional Echocardiography and CVIB
Statistical Analysis All data are expressed as mean ⫾ SD. Groups were compared for categoric data using the chi-square test and for continuous variables using 1-way analysis of variance with subsequent Scheffe´ multiple comparison. Differences were tested for significance using Student unpaired t test. A P value ⬍ .05 was considered significant.
Conventional echocardiographic parameters were similar in healthy participants and patients with PSS (Table 1). Moreover, global and regional (RV and LV halves of the septum, and endocardial and epicardial halves of the posterior wall) CVIB in patients with PSS was similar to that in healthy participants (Figure 1 and Table 2). Measurement of THIB
RESULTS Demographics, clinical, and serologic characteristics are summarized in Table 1. No significant differences were obtained between healthy participants and patients with PSS with respect to age, sex, and heart rate. Raynaud’s phenomenon and sclerodac-
A-THIB was greater in patients with PSS than in healthy participants (Table 2, Figures 1 and 2) in both the septum and posterior wall. Of particular interest, septal A-THIB was higher in patients with PSS who had anti-Scl70 or antinucleolar antibodies compared in those without either antibody (Table 3 and Figure 3).
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Table 2 Comparison of integrated backscatter parameters in healthy participants and patients with progressive systemic sclerosis
Global CVIB Septum (dB) PW (dB) Regional CVIB RV-half (dB) LV-half (dB) Endo-half (dB) Epi-half (dB) A-THIB Septum (dB) PW (dB)
Healthy participants
Patients with PSS
P value
7.3 ⫾ 0.6 7.5 ⫾ 1.3
7.2 ⫾ 0.9 7.8 ⫾ 1.4
NS NS
8.3 ⫾ 1.7 6.4 ⫾ 1.9 7.5 ⫾ 2.3 7.5 ⫾ 1.1
7.7 ⫾ 1.4 6.9 ⫾ 1.6 7.4 ⫾ 2.0 8.1 ⫾ 1.0
NS NS NS NS
1.3 ⫾ 1.3 1.1 ⫾ 0.7
4.0 ⫾ 1.4 2.8 ⫾ 0.4
.0002 .0001
Table 3 Comparison of transmural heterogeneity in myocardial integrated backscatter in patients with progressive systemic sclerosis
A-THIB Septum (dB) PW (dB)
Without autoantibodies
With autoantibodies
P value
3.2 ⫾ 1.1 2.8 ⫾ 0.4
5.0 ⫾ 1.0 3.0 ⫾ 0.4
.0165 NS
A-THIB, Absolute value of transmural heterogeneity in myocardial integrated backscatter; PW, posterior wall; NS, not significant.
CVIB, Magnitude of cyclic variation in integrated backscatter; PW, posterior wall; RV-half, right ventricular half of the septum; LV-half, left ventricular half of the septum; Endo-half, endocardial half of the posterior wall; Epi-half, epicardial half of the posterior wall; A-THIB, the absolute value of the difference of the transmural heterogeneity in myocardial integrated backscatter; NS, not significant. Values are expressed as mean ⫾ SD.
Figure 3 Comparison of absolute value of transmural heterogeneity in myocardial integrated backscatter (ATHIB) between patients who have progressive systemic sclerosis (PSS) with and without anti-Scl70 or antinucleolar antibodies. Septal A-THIB was greater in patients with than without autoantibodies. **P ⫽ .0165 vs without autoantibodies. PW, Posterior wall.
Figure 2 Comparison of absolute value of transmural heterogeneity in myocardial integrated backscatter (ATHIB) between healthy participants and patients with progressive systemic sclerosis (PSS). A-THIB was greater in patients with PSS than in healthy participants, in both septum and posterior wall (PW). *P ⬍ .0005 vs healthy participants.
DISCUSSION Previous studies have shown that the absolute IB and the magnitude of the CVIB reflect the acoustic properties of the myocardium, because the collagen content of the myocardium13,14 and myocardial fibrosis15 increase the absolute IB. Collagen may be an important determinant of backscatter. Furthermore,
it has been shown that the CVIB is affected by myocardial contractility16 and fiber architecture.5,17 Cardiac involvement in PSS is well documented and predicts poor prognosis.18 Because cardiac involvement is often clinically occult, the reported prevalence of cardiac disease varies depending on the methods used to define this entity. Therefore, this study explored the use of IB analysis to detect early ultrastructural changes in the sclerodermal myocardium. We hypothesized that the magnitude of CVIB in the subendocardial and LV halves would be larger than in the subepicardial and RV halves, because the contractility of the myocardium is a major determinants of CVIB, and the percent wall thickening of the subendocardial and LV halves are usually larger than that of the subepicardial and RV halves.19 Contrary to our expectation, there was no difference in global or regional (the RV and LV halves of the septum, and the endocardial and epicardial
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halves of the posterior wall) CVIB between healthy participants and patients with PSS. However, A-THIB in patients with PSS was greater than in healthy participants, and septal A-THIB was greatest in patients with anti-Scl70 or antinucleolar antibodies. These data suggest that early changes in the myocardium in PSS, related to occult cardiac involvement, may be detected by quantitative analysis of THIB.
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ment, particularly LV lesions, which present mainly as hypertrophy as a result of myocardial fibrosis that disturbs LV diastolic filling.24-27 Because A-THIB was greater in patients with PSS than in healthy participants even though conventional echocardiographic parameters were similar, THIB appears to reflect heterogeneity in the myocardium as a result of interstitial fibrosis that cannot be assessed by conventional echocardiography.
Myocardial Changes in PSS Although it has been estimated that sclerodermal heart disease is clinically manifest in only 20% to 25% of cases, the prognosis in these patients is extremely poor, and the mortality at 5 years is 70%.20 Furthermore, myocardial involvement has been documented in up to 81% of patients with PSS at autopsy.21,22 Bulkley et al2 reported that PSS myocardial involvement is characterized morphologically by a spectrum of myocardial injuries ranging from contraction band necrosis to fibrous replacement, and they hypothesized that the pathogenesis is intermittent spasm of the small coronary arteries, the so-called, myocardial Raynaud’s phenomenon. However, the exact mechanism leading to myocardial fibrosis remains unknown. Several clinical studies of myocardial involvement in PSS have been performed using conventional echocardiographic parameters, including ejection fraction, fractional shortening, peak E, peak A, E/A, deceleration time, and isovolumic relaxation time. However, abnormalities in these parameters were detected in only 11% to 32% of patients.20 Our data similarly found no difference between healthy participants and patients with PSS in conventional echocardiographic parameters, including Doppler analysis. Transmural Trend in the Acoustic Properties of the Myocardium Recent studies have shown that the transmural trend in the acoustic properties of the myocardium is different in patients with heart disease than in healthy individuals.5,9,23 We have suggested that measurement of the transmural trend in myocardial IB can differentiate between hypertrophic cardiomyopathy and LV hypertrophy as a result of hypertension, and that the difference in the trend in myocardial IB is reflected in transmural heterogeneity in both myocardial fibrosis and fiber disarray.5 And, it also has been documented that the values of the measurement of the transmural trend for the discrimination of infarcted myocardium, that is likely to reflect the transmurality of myocardial fibrosis.9,23 On histopathologic examination, the characteristic lesion appears as a region of myocardial fibrosis with involvement of the coronary microcirculation without narrowing of the extramural coronary arteries. Several investigators have studied cardiac involve-
Advantage of Measuring THIB This method does not require normalization of signals by comparison with a reference material because the parameter is generated by assessing differences in each area of interest along a single interrogating beam. Some studies have used the pericardial surface to calibrate myocardial IB.4 However, this calibration method is inherently affected by pericardial thickening or specular pericardial echoes. The specular echo is sensitive to the details of insonification, such as angle dependency or saturation of the front-end electronics from pericardial signals, and may be observed even in the absence of pathologic changes in the pericardium. We believe that our method is free of such limitations. Comparison with Previous Studies Murata et al28 demonstrated that LV fractional shortening is smaller in patients with PSS with diffuse cutaneous involvement or anti-Scl70 antibodies. Furthermore, a few studies have evaluated cardiac involvement in PSS by ultrasonic tissue characterization.29,30 Ferri et al29 and Di Bello et al30 reported that CVIB obtained from videodensitometric analysis was lower in patients with PSS than in healthy participants and concluded that the increased incidence of this abnormality reflects changes in myocardial structure, even in the preclinical phase. However, some differences exist between those studies and ours. In this study, all patients, even those with autoantibodies, had normal systolic function as determined by conventional echocardiography. The normal level of CVIB in patients with PSS also suggests that contractility was normal, because it has been supported that CVIB reflects the dynamic properties in the myocardium.16 Then, our patients did not have any abnormalities in parameters of diastolic function, such as E/A. Although the studies by Ferri et al29 and Di Bello et al30 concluded that reduced CVIB might reflect the presence of myocardial structural abnormalities, their patients had lower E/A compared with healthy participants, and diastolic dysfunction might have reduced CVIB. Furthermore, our data showed not only that CVIB was similar in healthy participants and patients with PSS, as opposed to previous findings, but also that THIB was greater in patients with PSS than in healthy participants. Accordingly, THIB may be suf-
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ficiently sensitive to detect changes in myocardial structure, even in the preclinical phase of PSS. Myocardial involvement has been reported to be more common and severe in patients with diffuse rather than limited cutaneous involvement.31 This study did not address the issue specifically. However, other recent studies focusing on cardiac involvement in limited cutaneous PSS have demonstrated a high percentage of cardiovascular abnormalities in these patients using noninvasive techniques, even though the incidence of cardiac symptoms is low.32 It has been reported that myocardial fibrosis occurs predominantly in patients with diffuse cutaneous disease, in whom anti-Scl70 and antinucleolar antibodies are present.2,33 Our data show that THIB is higher in patients with PSS with than without anti-Scl70 or antinucleolar antibodies. Thus, it appears that myocardial involvement is more severe when anti-Scl70 antibodies, antinucleolar antibodies, or both are present, although the role of serum autoantibodies in the pathogenesis of PSS has not yet been determined. Study Limitations CVIB is dependent on the angle between fiber orientation and ultrasonic beam, called anisotoropy.34-37 Data in this study were obtained only from the septum and posterior regions in the parasternal long-axis views in which myocardial fiber of these segments is oriented nearly perpendicular to the ultrasound beam. Another method such as magnetic resonance imaging may be favorable to characterize the myocardial tissue composition in the lateral and medial walls.
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CONCLUSIONS CVIB is similar in healthy participants and patients with PSS, but THIB is greater in patients with PSS. This finding suggests that early changes in the myocardium in PSS, possibly related to increased interstitial collagen deposition, can be detected by quantitative analysis of THIB, and that THIB may be a useful parameter for assessing myocardial involvement in PSS and may predict subsequent development of myocardial fibrosis.
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19. Bombardini T, Galli R, Paterni M, Pingitore A, Pierangeli A, Picano E. A videodensitometric study of transmural heterogeneity of cyclic echo amplitude variation in human myocardium. Am J Cardiol 1996;78:212-6. 20. Deswal A, Follansbee WP. Cardiac involvement in scleroderma. Rheum Dis Clin North Am 1996;22:841-60. 21. D’Angelo WA, Fries JF, Masi AT, Shulman LE. Pathologic observations in systemic sclerosis (scleroderma): a study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 1969;46:428-40. 22. Follansbee WP, Miller TR, Curtiss EI, Orie JE, Bernstein RL, Kiernan JM, et al. A controlled clinicopathologic study of myocardial fibrosis in systemic sclerosis (scleroderma). J Rheumatol 1990;17:656-62. 23. Wickline SA, Verdonk ED, Wong AK, Shepard RK, Miller JG. Structural remodeling of human myocardial tissue after infarction: quantification with ultrasonic backscatter. Circulation 1992;85:259-68. 24. Butrous GS, Dowd PM, Milne J, Dymond DS, Caplin J, Camm AJ. Non-invasive assessment of early cardiac involvement in systemic sclerosis. Postgrad Med J 1985;61:679-84. 25. Smith JW, Clements PJ, Levisman J, Furst D, Ross M. Echocardiographic features of progressive systemic sclerosis (PSS): correlation with hemodynamic and postmortem studies. Am J Med 1979;66:28-33. 26. Kazzam E, Caidahl K, Hallgren R, Gustafsson R, Landelius J, Waldenstrom A. Non-invasive assessment of systolic left ventricular function in systemic sclerosis. Eur Heart J 1991;12: 151-6. 27. Kazzam E, Caidahl K, Hallgren R, Johansson C, Waldenstrom A. Mitral regurgitation and diastolic flow profile in systemic sclerosis. Int J Cardiol 1990;29:357-63. 28. Murata I, Takenaka K, Shinohara S, Suzuki T, Sasaki T, Yamamoto K. Diversity of myocardial involvement in systemic sclerosis: an 8-year study of 95 Japanese patients. Am Heart J 1998;135:960-9.
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29. Ferri C, Di Bello V, Martini A, Giorgi D, Storino FA, Bianchi M, et al. Heart involvement in systemic sclerosis: an ultrasonic tissue characterisation study. Ann Rheum Dis 1998;57:296302. 30. Di Bello V, Ferri C, Giorgi D, Bianchi M, Bertini A, Martini A, et al. Ultrasonic videodensitometric analysis in scleroderma heart disease. Coron Artery Dis 1999;10:103-10. 31. Follansbee WP, Curtiss EI, Medsger TA Jr, Owens GR, Steen VD, Rodnan GP. Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis: exercise radionuclide evaluation and comparison with diffuse scleroderma. Am J Med 1984;77:489-96. 32. Candell-Riera J, Armadans-Gil L, Simeon CP, Castell-Conesa J, Fonollosa-Pla V, Garcia-del-Castillo H, et al. Comprehensive noninvasive assessment of cardiac involvement in limited systemic sclerosis. Arthritis Rheum 1996;39:1138-45. 33. Follansbee WP, Curtiss EI, Medsger TA Jr, Steen VD, Uretsky BF, Owens GR, et al. Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma. N Engl J Med 1984;310:142-8. 34. Streeter DD Jr, Spotnitz HM, Patel DP, Ross J Jr, Sonnenblick EH. Fiber orientation in the canine left ventricle during diastole and systole. Circ Res 1969;24:339-47. 35. Aygen M, Popp RL. Influence of the orientation of myocardial fibers on echocardiographic images. Am J Cardiol 1987; 60:147-52. 36. Holland MR, Wilkenshoff UM, Finch-Johnston AE, Handley SM, Perez JE, Miller JG. Effects of myocardial fiber orientation in echocardiography: quantitative measurements and computer simulation of the regional dependence of backscattered ultrasound in the parasternal short-axis view. J Am Soc Echocardiogr 1998;11:929-37. 37. Finch-Johnston AE, Gussak HM, Mobley J, Holland MR, Petrovic O, Perez JE, et al. Cyclic variation of integrated backscatter: dependence of time delay on the echocardiographic view used and the myocardial segment analyzed. J Am Soc Echocardiogr 2000;13:9-17.
Cardiac involvement in progressive systemic sclerosis (PSS) is common and has a strong negative impact on the prognosis, especially when autoantibodies are present. To determine whether ultrasonic tissue characterization can detect early ultrastructural changes in the sclerodermal myocardium, we analyzed the transmural heterogeneity in myocardial integrated backscatter (THIB). “A-THIB” was defined as the absolute difference in integrated backscatter between the left (subendocardial) and right (subepicardial) ventricular halves of the myocardium in the septum and posterior wall, and was measured in 11 patients with PSS and 10 age- and
Progressive systemic sclerosis (PSS) is a connective
tissue disease characterized by overproduction of collagen and its deposition in multiple organs, including the skin, lung, kidney, gastrointestinal tract, and heart.1 Myocardial fibrosis is the most common cardiac lesion in PSS, occurring in up to 50% of patients.2 Because cardiac involvement is one of the most frequent complications and strongly affects the overall prognosis, early detection and monitoring of myocardial involvement may decide therapeutic strategies. Myocardial integrated backscatter (IB) is a noninvasively determined parameter of the acoustic properties of myocardium and previously has been shown to reflect physiologic conditions, pathologic conditions, or both in the myocardium.3-9 Recent studies have suggested that the transmural trend in myocardial IB reflects the transmural heterogeneity From the Cardiovascular Divisions of Osaka National Hospital and Osaka Police Hospital (J.N.); and Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine (M.H.). Presented in part at the 13th Annual Scientific Sessions of the American Society of Echocardiography, June 2002, Orlando, Fla. Reprint requests: Keiji Hirooka, MD, PhD, Cardiovascular Division, Osaka National Hospital, 2-1-14, Hoenzaka, Chuo-ku, 5400006, Osaka, Japan (E-mail: [email protected]). Copyright 2003 by the American Society of Echocardiography. 0894-7317/2003/$30.00 ⫹ 0 doi:10.1016/S0894-7317(02)74427-1
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sex-matched healthy participants. A-THIB in patients with PSS was higher than that in healthy participants (1.3 ⴞ 1.3 vs 4.0 ⴞ 1.4 dB for the septum and 1.1 ⴞ 0.7 dB vs 2.8 ⴞ 0.4 dB for the posterior wall; mean ⴞ SD, respectively, P < .0005). Septal A-THIB was higher in patients with PSS with than without anti-Scl70 or antinucleolar antibodies (3.2 ⴞ 1.1 vs 5.0 ⴞ 1.0 dB, P ⴝ .0165). Early changes in the myocardium of patients with PSS, possibly related to increased interstitial collagen deposition, can be detected by quantitative analysis of THIB. (J Am Soc Echocardiogr 2003;16:340-6.)
of myocardial fibrosis and viability, in addition to quantifying the magnitude of cardiac cycle-dependent variation in IB.5,9 The purpose of this study was to clarify whether analysis of transmural heterogeneity in myocardial IB (THIB) can be used to detect early ultrastructural changes in the sclerodermal myocardium.
METHODS Patients The study population consisted of 11 patients who received a diagnosis of PSS on the basis of the criteria of the American Rheumatism Association.10 Patients with PSS were recruited from the collagen disease center of the Department of Dermatology at Osaka National Hospital. The mean duration of disease was 99.5 months (range, 24 to 240 months). Of this group, 7 patients had limited cutaneous type and 4 patients had diffuse cutaneous involvement. None of the patients had valvular heart disease, congenital heart disease, left ventricular (LV) hypertrophy, heart failure, or prior myocardial infarction, and none were taking cardioactive drugs. No electrocardiographic abnormalities were present at rest in any participant. Patients with respiratory failure, renal insufficiency, diabetes mellitus, or hypertension were excluded from the study. All patients in the study were clinically stable. As control participants, we evaluated 10 age- and
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sex-matched healthy volunteers who had no clinical, electrocardiographic, or radiographic evidence of heart disease. All patients had the serologic autoantibodies specific for PSS, anti-Scl70, antinucleolar, and anticentromere antibody, measured using standard techniques.10,11 All participants gave informed consent for participation in the study, which was approved by our institutional ethics committee. Conventional Echocardiography Before the IB study, all participants were examined using conventional 2-dimensional and M-mode echocardiography with Doppler analysis, to assess chamber size, wall thickness, wall motion, and the pulsed Doppler transmitral inflow velocities. Echocardiographic variables were measured in a standard manner by parasternal views.12 The pulsed Doppler transmitral inflow velocities were obtained from an apical 4-chamber view, and the Doppler sample volume was placed on the tips of the mitral leaflets to analyze the peak early diastolic LV filling velocity (peak E), the peak LV filling velocity during atrial contraction (peak A), the ratio of peak E to peak A (E/A), the deceleration time, and the isovolumic relaxation time. The Doppler recordings were made at a paper speed of 100 mm/s. The deceleration time was calculated by estimating the period from the peak early diastolic LV filling velocity to an extrapolation of the deceleration of flow to baseline. The “isovolumic relaxation time” was defined as the interval between closure of the aortic valve and the onset of the mitral flow. Ultrasonic Backscatter Instrumentation The IB imaging system consisted of a commercially available ultrasound system (SSD-2200; Aloka Co Ltd, Tokyo, Japan) with a 2.5-MHz frequency transducer. With this system, either conventional 2-dimensional and M-mode echo amplitude or the IB of myocardium using the power of tissue Doppler can be obtained. Unlike a conventional imaging system, however, the ultrasound signals are accessed with IB processor to produce a continuous signal that is proportional to the logarithm of IB in the power of tissue Doppler. The value of myocardial IB (IBc) is expressed as the power of the ultrasound backscattered from the myocardium in conventional imaging mode.5,7-9 IBc ⫽
冕
⫹⌬ ⫺⌬
兩m(t)兩2 dt
(1)
where m(t) is the signal received from the tissue (myocardium); is the position in time of the center of the region of interest (ROI); and ⌬ is the corresponding half-width in time. The value of myocardial IB (IBp) is obtained from the myocardium by measuring the power of the received radiofrequency signal. IBp ⫽
1 n
冘 n
k⫽1
关兵I' k共t兲其 2 ⫹ 兵Q' k共t兲其 2兴
(2)
where I ' (t) and Q' (t) are the real part and imaginary parts of the quadrature detector outputs, respectively; k represents the kth receipt for the same raster; and n is the packet size. IBp is calculated from the spatial integral of the signals, whereas IBc is the pure time integral. However, there is no essential difference between IBc and IBp because IB is obtained by measuring the average of signals in a ROI, and IBp is determined by measuring the average of signals over a period. The period is 4 ⫻ 1/4000 ⫽ 1 millisecond, because the pulse repetition frequency is 4 kHz and the packet size is 4 in this method. The variation in IB can be ignored within this period, therefore, IBp corresponds closely enough to IBc to assume equivalency. We carefully adjusted the time-gain controls in each patient to produce a uniform brightness of the myocardium without saturation. Data Analysis of Myocardial IB Subsequent to the conventional echocardiography, the IB study was performed by tracing the ROI along frozen M-mode images from the parasternal long-axis view. The ROI for backscatter measurements was traced midway between the endocardial and epicardial borders of the septum and posterior wall. We attempted to exclude the thick, bright lines of the endocardium and intramyocardial specular bright echoes from the ROI. The depth of the ROI was 5 mm in this study. After placing the ROI for backscatter measurements in the M-mode IB images, curves of myocardial IB were created. The magnitude of cyclic variation in IB (CVIB) was determined from these curves, as the difference between the minimum and maximum values. Because the monitor can display on 1 screen for 2500 seconds, we analyzed using the averaged values of 2 to 4 cardiac cycles according to the patient’s heart rate. Furthermore, this system calculates myocardial IB of both the distal and proximal halves in the ROI (the LV and right ventricular [RV] halves of the septum, and the epicardial and endocardial halves of the posterior wall) (Figure 1). We measured the THIB to evaluate the transmural trend of acoustic properties in myocardium. THIB measures the difference in IB (not the difference in the magnitude of CVIB) between the distal and proximal halves in the same ROI. Therefore, if the IB from subendocardial region of the posterior wall is much larger than the IB from the adjacent subepicardial region, then the THIB would be relatively large and positive. If, on the other hand, the IB from subendocardial region of the posterior wall is much smaller than the IB from the adjacent subepicardial region, then the THIB would be relatively large but negative. In this study, however, we evaluated the absolute value of the difference of the THIB (A-THIB) only to estimate the extent of the dispersion in THIB. With this system, A-THIB can be determined automatically in IB in the unit decibels (dB). It has been noted that this determination does not require calibration because the measurement in the same ROI along the same interrogating beam corrects for signal or attenuation loss
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Table 1 Comparison of demographics, clinical characteristics, and conventional echocardiographic parameters in healthy participants and patients with progressive systemic sclerosis Healthy Patients with participants PSS
Figure 1 Myocardial integrated backscatter (IB) image of septum of healthy participant (A) and of patient with progressive systemic sclerosis (PSS) (B) from parasternal long-axis view. M-mode myocardial IB image of left ventricle (LV) with trace of region of interest (ROI) (lower), global (upper), and regional (middle) curves of septal IB. Global and regional (upper vs lower half) magnitude of cyclic variation in IB were similar in healthy participants and patients with PSS, but transmural heterogeneity in myocardial IB was greater in patient with PSS (zoom-in view). Yellow line, Right ventricular half; green line, LV half; ECG, electrocardiogram.
resulting from transmission through tissue intervening between the transducer and the ROI.5 Data Reproducibility We determined intraobserver and interobserver variabilities in CVIB in 10 randomly selected records on the basis of observations by the same observer and by 2 independent observers, respectively. Absolute differences in global CVIB between observations were 0.6 ⫾ 0.7 dB (intraobserver) and 0.9 ⫾ 0.6 dB (interobserver) for the septum, and 0.8 ⫾ 0.7 dB (intraobserver) and 1.1 ⫾ 0.8 dB (interobserver) for the posterior wall.
No. of participants Age (y) Sex HR (bpm) LAD (mm) IVSth (mm) PWth (mm) LVDd (mm) LVDs (mm) FS (%) IVRT (ms) E (cm/s) A (cm/s) E/A DcT (ms) Autoantibodies Anti-Scl70 antibody Antinucleolar antibody Anticentromere antibody
10 54 ⫾ 15 9 F, 1 M 68 ⫾ 12 36.7 ⫾ 4.2 8.8 ⫾ 0.9 8.6 ⫾ 0.8 45.6 ⫾ 2.3 27.0 ⫾ 2.2 40.7 ⫾ 5.5 76.0 ⫾ 22.7 77.4 ⫾ 20.9 72.9 ⫾ 23.8 1.13 ⫾ 0.36 245 ⫾ 58
11 (7L, 4D) 52 ⫾ 8 10 F, 1 M 82 ⫾ 19 37.0 ⫾ 3.4 9.5 ⫾ 1.3 9.1 ⫾ 0.8 44.5 ⫾ 4.3 23.9 ⫾ 5.6 45.1 ⫾ 8.9 84.7 ⫾ 10.6 72.7 ⫾ 6.2 75.2 ⫾ 25.9 1.09 ⫾ 0.41 224 ⫾ 40
P value
P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS P ⫽ NS
4 (36%) 3 (27%) 2 (18%)
L, Limited cutaneous type; D, diffuse cutaneous type; F, female; M, male; HR, heart rate; LAD, left atrial diameter at end-systole; PSS, progressive systemic sclerosis; NS, not significant; IVSth, wall thickness of septum at end-diastole; PWth, wall thickness of posterior wall at end-diastole; LVDd, left ventricular diameter at end-diastole; LVDs, left ventricular diameter at end-systole; FS, fractional shortening; IVRT, isovolumic relaxation time; E, peak early diastolic left ventricular filling velocity; A, peak left ventricular filling velocity during atrial contraction; E/A, ratio of peak early diastolic filling velocity to peak filling velocity during atrial contraction; DcT, deceleration time. Values are expressed as mean ⫾ SD.
tyly were seen in all patients, whereas dysphagia was seen in 5 patients. Arthralgias were present in 6, arthritis in 1, calcinosis in 2, and telangiectasias in 7 patients. Two patients whose anticentromere antibodies were positive in limited cutaneous PSS were considered to have CREST syndrome. Conventional Echocardiography and CVIB
Statistical Analysis All data are expressed as mean ⫾ SD. Groups were compared for categoric data using the chi-square test and for continuous variables using 1-way analysis of variance with subsequent Scheffe´ multiple comparison. Differences were tested for significance using Student unpaired t test. A P value ⬍ .05 was considered significant.
Conventional echocardiographic parameters were similar in healthy participants and patients with PSS (Table 1). Moreover, global and regional (RV and LV halves of the septum, and endocardial and epicardial halves of the posterior wall) CVIB in patients with PSS was similar to that in healthy participants (Figure 1 and Table 2). Measurement of THIB
RESULTS Demographics, clinical, and serologic characteristics are summarized in Table 1. No significant differences were obtained between healthy participants and patients with PSS with respect to age, sex, and heart rate. Raynaud’s phenomenon and sclerodac-
A-THIB was greater in patients with PSS than in healthy participants (Table 2, Figures 1 and 2) in both the septum and posterior wall. Of particular interest, septal A-THIB was higher in patients with PSS who had anti-Scl70 or antinucleolar antibodies compared in those without either antibody (Table 3 and Figure 3).
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Table 2 Comparison of integrated backscatter parameters in healthy participants and patients with progressive systemic sclerosis
Global CVIB Septum (dB) PW (dB) Regional CVIB RV-half (dB) LV-half (dB) Endo-half (dB) Epi-half (dB) A-THIB Septum (dB) PW (dB)
Healthy participants
Patients with PSS
P value
7.3 ⫾ 0.6 7.5 ⫾ 1.3
7.2 ⫾ 0.9 7.8 ⫾ 1.4
NS NS
8.3 ⫾ 1.7 6.4 ⫾ 1.9 7.5 ⫾ 2.3 7.5 ⫾ 1.1
7.7 ⫾ 1.4 6.9 ⫾ 1.6 7.4 ⫾ 2.0 8.1 ⫾ 1.0
NS NS NS NS
1.3 ⫾ 1.3 1.1 ⫾ 0.7
4.0 ⫾ 1.4 2.8 ⫾ 0.4
.0002 .0001
Table 3 Comparison of transmural heterogeneity in myocardial integrated backscatter in patients with progressive systemic sclerosis
A-THIB Septum (dB) PW (dB)
Without autoantibodies
With autoantibodies
P value
3.2 ⫾ 1.1 2.8 ⫾ 0.4
5.0 ⫾ 1.0 3.0 ⫾ 0.4
.0165 NS
A-THIB, Absolute value of transmural heterogeneity in myocardial integrated backscatter; PW, posterior wall; NS, not significant.
CVIB, Magnitude of cyclic variation in integrated backscatter; PW, posterior wall; RV-half, right ventricular half of the septum; LV-half, left ventricular half of the septum; Endo-half, endocardial half of the posterior wall; Epi-half, epicardial half of the posterior wall; A-THIB, the absolute value of the difference of the transmural heterogeneity in myocardial integrated backscatter; NS, not significant. Values are expressed as mean ⫾ SD.
Figure 3 Comparison of absolute value of transmural heterogeneity in myocardial integrated backscatter (ATHIB) between patients who have progressive systemic sclerosis (PSS) with and without anti-Scl70 or antinucleolar antibodies. Septal A-THIB was greater in patients with than without autoantibodies. **P ⫽ .0165 vs without autoantibodies. PW, Posterior wall.
Figure 2 Comparison of absolute value of transmural heterogeneity in myocardial integrated backscatter (ATHIB) between healthy participants and patients with progressive systemic sclerosis (PSS). A-THIB was greater in patients with PSS than in healthy participants, in both septum and posterior wall (PW). *P ⬍ .0005 vs healthy participants.
DISCUSSION Previous studies have shown that the absolute IB and the magnitude of the CVIB reflect the acoustic properties of the myocardium, because the collagen content of the myocardium13,14 and myocardial fibrosis15 increase the absolute IB. Collagen may be an important determinant of backscatter. Furthermore,
it has been shown that the CVIB is affected by myocardial contractility16 and fiber architecture.5,17 Cardiac involvement in PSS is well documented and predicts poor prognosis.18 Because cardiac involvement is often clinically occult, the reported prevalence of cardiac disease varies depending on the methods used to define this entity. Therefore, this study explored the use of IB analysis to detect early ultrastructural changes in the sclerodermal myocardium. We hypothesized that the magnitude of CVIB in the subendocardial and LV halves would be larger than in the subepicardial and RV halves, because the contractility of the myocardium is a major determinants of CVIB, and the percent wall thickening of the subendocardial and LV halves are usually larger than that of the subepicardial and RV halves.19 Contrary to our expectation, there was no difference in global or regional (the RV and LV halves of the septum, and the endocardial and epicardial
344 Hirooka et al
halves of the posterior wall) CVIB between healthy participants and patients with PSS. However, A-THIB in patients with PSS was greater than in healthy participants, and septal A-THIB was greatest in patients with anti-Scl70 or antinucleolar antibodies. These data suggest that early changes in the myocardium in PSS, related to occult cardiac involvement, may be detected by quantitative analysis of THIB.
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ment, particularly LV lesions, which present mainly as hypertrophy as a result of myocardial fibrosis that disturbs LV diastolic filling.24-27 Because A-THIB was greater in patients with PSS than in healthy participants even though conventional echocardiographic parameters were similar, THIB appears to reflect heterogeneity in the myocardium as a result of interstitial fibrosis that cannot be assessed by conventional echocardiography.
Myocardial Changes in PSS Although it has been estimated that sclerodermal heart disease is clinically manifest in only 20% to 25% of cases, the prognosis in these patients is extremely poor, and the mortality at 5 years is 70%.20 Furthermore, myocardial involvement has been documented in up to 81% of patients with PSS at autopsy.21,22 Bulkley et al2 reported that PSS myocardial involvement is characterized morphologically by a spectrum of myocardial injuries ranging from contraction band necrosis to fibrous replacement, and they hypothesized that the pathogenesis is intermittent spasm of the small coronary arteries, the so-called, myocardial Raynaud’s phenomenon. However, the exact mechanism leading to myocardial fibrosis remains unknown. Several clinical studies of myocardial involvement in PSS have been performed using conventional echocardiographic parameters, including ejection fraction, fractional shortening, peak E, peak A, E/A, deceleration time, and isovolumic relaxation time. However, abnormalities in these parameters were detected in only 11% to 32% of patients.20 Our data similarly found no difference between healthy participants and patients with PSS in conventional echocardiographic parameters, including Doppler analysis. Transmural Trend in the Acoustic Properties of the Myocardium Recent studies have shown that the transmural trend in the acoustic properties of the myocardium is different in patients with heart disease than in healthy individuals.5,9,23 We have suggested that measurement of the transmural trend in myocardial IB can differentiate between hypertrophic cardiomyopathy and LV hypertrophy as a result of hypertension, and that the difference in the trend in myocardial IB is reflected in transmural heterogeneity in both myocardial fibrosis and fiber disarray.5 And, it also has been documented that the values of the measurement of the transmural trend for the discrimination of infarcted myocardium, that is likely to reflect the transmurality of myocardial fibrosis.9,23 On histopathologic examination, the characteristic lesion appears as a region of myocardial fibrosis with involvement of the coronary microcirculation without narrowing of the extramural coronary arteries. Several investigators have studied cardiac involve-
Advantage of Measuring THIB This method does not require normalization of signals by comparison with a reference material because the parameter is generated by assessing differences in each area of interest along a single interrogating beam. Some studies have used the pericardial surface to calibrate myocardial IB.4 However, this calibration method is inherently affected by pericardial thickening or specular pericardial echoes. The specular echo is sensitive to the details of insonification, such as angle dependency or saturation of the front-end electronics from pericardial signals, and may be observed even in the absence of pathologic changes in the pericardium. We believe that our method is free of such limitations. Comparison with Previous Studies Murata et al28 demonstrated that LV fractional shortening is smaller in patients with PSS with diffuse cutaneous involvement or anti-Scl70 antibodies. Furthermore, a few studies have evaluated cardiac involvement in PSS by ultrasonic tissue characterization.29,30 Ferri et al29 and Di Bello et al30 reported that CVIB obtained from videodensitometric analysis was lower in patients with PSS than in healthy participants and concluded that the increased incidence of this abnormality reflects changes in myocardial structure, even in the preclinical phase. However, some differences exist between those studies and ours. In this study, all patients, even those with autoantibodies, had normal systolic function as determined by conventional echocardiography. The normal level of CVIB in patients with PSS also suggests that contractility was normal, because it has been supported that CVIB reflects the dynamic properties in the myocardium.16 Then, our patients did not have any abnormalities in parameters of diastolic function, such as E/A. Although the studies by Ferri et al29 and Di Bello et al30 concluded that reduced CVIB might reflect the presence of myocardial structural abnormalities, their patients had lower E/A compared with healthy participants, and diastolic dysfunction might have reduced CVIB. Furthermore, our data showed not only that CVIB was similar in healthy participants and patients with PSS, as opposed to previous findings, but also that THIB was greater in patients with PSS than in healthy participants. Accordingly, THIB may be suf-
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ficiently sensitive to detect changes in myocardial structure, even in the preclinical phase of PSS. Myocardial involvement has been reported to be more common and severe in patients with diffuse rather than limited cutaneous involvement.31 This study did not address the issue specifically. However, other recent studies focusing on cardiac involvement in limited cutaneous PSS have demonstrated a high percentage of cardiovascular abnormalities in these patients using noninvasive techniques, even though the incidence of cardiac symptoms is low.32 It has been reported that myocardial fibrosis occurs predominantly in patients with diffuse cutaneous disease, in whom anti-Scl70 and antinucleolar antibodies are present.2,33 Our data show that THIB is higher in patients with PSS with than without anti-Scl70 or antinucleolar antibodies. Thus, it appears that myocardial involvement is more severe when anti-Scl70 antibodies, antinucleolar antibodies, or both are present, although the role of serum autoantibodies in the pathogenesis of PSS has not yet been determined. Study Limitations CVIB is dependent on the angle between fiber orientation and ultrasonic beam, called anisotoropy.34-37 Data in this study were obtained only from the septum and posterior regions in the parasternal long-axis views in which myocardial fiber of these segments is oriented nearly perpendicular to the ultrasound beam. Another method such as magnetic resonance imaging may be favorable to characterize the myocardial tissue composition in the lateral and medial walls.
Hirooka et al 345
4.
5.
6.
7.
8.
9.
10.
11.
12.
CONCLUSIONS CVIB is similar in healthy participants and patients with PSS, but THIB is greater in patients with PSS. This finding suggests that early changes in the myocardium in PSS, possibly related to increased interstitial collagen deposition, can be detected by quantitative analysis of THIB, and that THIB may be a useful parameter for assessing myocardial involvement in PSS and may predict subsequent development of myocardial fibrosis.
13.
14.
15.
16.
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