(Circulation. 1996;94:2826-2830.)
© 1996 American Heart Association, Inc.
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the Facolta di Medicina Federico II, Cattedra di Geriatria (D.F.V., G.G., C.B., C.R., F.R.), Cattedra di Cardiologia Pediatrica (R.C., G.P., P.C.), and Cattedra di Cardiologia (M.A.L.), Naples, and Divisione di Cardiologia, Ospedali Riuniti (M. De C.), Salerno, Italy, and Northwestern University Medical School, Division of Cardiology, Chicago, Ill (R.O.B.).
Correspondence to Dino F. Vitale, MD, Cattedra di Geriatria, via S Pansini 5, 80131 Naples, Italy.
| Abstract |
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Methods and Results Sixty-eight subjects underwent backscatter analysis to assess the ultrasonic myocardial reflectivity and the amplitude of the cardiac cycledependent variation of the backscatter power curve. Subjects were divided into four groups: 10 HCM and 23 normal subjects <10 years old and 17 HCM and 18 normal adults. Myocardial reflectivity and amplitude of the cyclic variation were assessed in the septum and in the posterior wall of all subjects. The children with HCM were restudied after long-term oral administration of verapamil. Both children and adult patients, compared with the normal control groups, showed a significant reduction in the amplitude of the cyclic variation both in the septum and in the posterior wall. In contrast, myocardial reflectivity, although significantly increased in adult HCM patients, was unchanged in the young HCM group. Verapamil administration did not significantly alter the results in the children with HCM.
Conclusions These data demonstrate that in young HCM patients, the ultrasonic myocardial reflectivity is normal, in contrast to the significant increase observed in adult patients affected by the same disease. This observation is in accord with the different clinical manifestations reported in young HCM patients and indicates an age-dependent difference in the echogenic structure of the hypertrophied myocardium in HCM.
Key Words: hypertrophy collagen
| Introduction |
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| Methods |
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10 years old. The ages (mean±SD) of the two groups of HCM patients were 4.8±3.7 and 30±16 years, respectively, and those of the normal subjects were 5.8±3.1 and 33±12 years, respectively. All children with HCM were asymptomatic, whereas 5 of 17 adults (29%) with HCM had mild to moderate symptoms characterized by palpitation, fatigue, and in 3 of the 5, effort chest pain. In 4 of the 10 children with HCM (40%) and in 10 of the 17 adults with HCM (60%), asymmetrical hypertrophy (ratio of septal to posterior wall thickness,
1.3) was present. Outflow tract obstruction was evaluated by the magnitude and duration of the systolic anterior motion of the mitral valve.12 13 14 Anterior leafletseptum contact for >30% of systole was present in 40% (4 of 10) of the children and 29% (6 of 17) of the adults with HCM. Ultrasound studies were performed while all patients with HCM were receiving no medications. The children with HCM then underwent repeat studies after oral administration of verapamil (0.5 mg·kg-1·d-1 in three divided doses) for at least 3 weeks (minimum, 3 weeks; maximum, 10 weeks; mean, 5.6±2.5 weeks). In the second study, care was exercised to explore the same myocardial region as in the initial study. All subjects gave informed consent to the study, and parental permission was obtained for the children.
Backscatter Data Acquisition and Analysis
The procedure used in this study has been described elsewhere.7 15 Briefly, ultrasound studies were performed with a Hewlett-Packard system (77020A) equipped with a 3.5-MHz transducer and connected with an HP A900 minicomputer to digitize (16.7-MHz sampling rate) and store the radiofrequency (RF) signal (42 dB dynamic range) of two-dimensional scans (30-Hz frame rate) for offline processing. All studies were performed in the parasternal long-axis view with time-gain control adjusted to have equal gain at each depth. After the initial adjustment, an acquisition test was made to pilot the adjustments of the transmit and gain controls to ensure that the greater amplitude of the RF signal relative to the midmyocardial region (occurring during diastole) was just below the saturation level and, consequently, the minimum amplitude value (occurring during systole) was still above the low signal level. Once adjusted, all controls were held constant during the study. In each study, a window encompassing only a portion of the myocardial wall was selected, as shown in Fig 1
. Two windows were selected in each study for each patient, one encompassing the septum and the other encompassing the posterior wall. Window dimensions ranged from 10 to 15 lines (0.5 to 2.0 cm), and each line was 2.0 to 3.0 cm long, with a resolution of
200 points per centimeter (given the speed of sound in tissue =1540 m/s and a sampling rate of 16.7 MHz).
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The recorded occurrence of the ECG R wave was used as a reference to average the corresponding power values derived from the RF data of the 15 to 20 cardiac cycles acquired for each study set. All cardiac cycles that were 33 ms longer or shorter than the mean cardiac cycle length were rejected from the averaging. Developed software allowed the reconstruction of image frames from the RF data to draw, in each frame of the mean cardiac cycle, areas of interest delimiting the midmyocardial zone of the wall. With only the RF data corresponding to each midmyocardial region of interest, a backscatter power curve was generated spanning a single cardiac cycle, with duration equal to the mean RR interval and with points representing the backscatter power value integrated over a midmyocardial area and averaged over several RR intervals (Fig 1
). To obtain power values, the original RF amplitude was rectified and then squared. The described averaging was performed after rectification and before squaring. Backscatter power curve values were normalized by the average power of the cardiac cycle, and this ratio was expressed in decibels.
From the same midmyocardial region of interest and from a region of interest drawn to include only the pericardium, the absolute values of the amplitude of the backscattered signal, integrated over the relative region of interest and averaged over the time of the mean cardiac cycle, were computed, and this time-averaged myocardial backscatter amplitude was expressed as a percentage of the pericardial integrated backscatter value and was used as a measure of the "myocardial reflectivity."10 Twice, the backscatter power curve amplitude of the first harmonic Fourier fitting has been used as a measure of the cyclic variation (Fig 2
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Diastolic wall thickness and systolic wall thickening, expressed as percentages of the diastolic measure, were recorded for both septum and posterior wall by use of standard criteria.16
Reproducibility of Data
Reproducibility of these parameters has been assessed in 20 subjects, with the backscatter study repeated within 24 hours from a first study. The two studies of each patient were analyzed by two different operators. Interstudy variability for the amplitude of the fundamental Fourier harmonic was 0.25 dB evaluated by regression analysis residual error and by SD of interstudy differences. The interstudy variability and residual error of time-averaged backscatter amplitude, as a percentage of the pericardial value, was 4.8%.
Statistical Analysis
All data are expressed as mean±SD. Comparisons between before and after administration of verapamil in children with HCM was performed by the paired Student's t test. Multiple comparisons between HCM versus normal subjects and children versus adult groups were performed by ANOVA with the Tukey method for multiple comparisons. Correlation between parameters was assessed by linear regression analysis.
| Results |
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The myocardial reflectivity of the septum and the posterior wall in children with HCM was not significantly different from that of the normal control group (26.2±8.7% versus 28.7±9.3%, P=NS, and 18.5±6.7% versus 20.3±6.9%, P=NS, respectively). However, the adult patients with HCM manifested a significantly greater reflectivity than normal control subjects, both in the septum and in the posterior wall (53.7±19.5% versus 30.2±9.4%, P<.01, and 36.2±12.2% versus 19.5±5.5%, P<.01) (Fig 6
). Congruent with these results, the myocardial reflectivity of the adult HCM patients was significantly greater than that of the children both in the septum and in the posterior wall. Both septal and posterior wall thicknesses were significantly higher in HCM subjects (adults and children) than in the normal control groups, and systolic wall thickening was significantly lower (Table
).
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The relation between the backscatter parameters (reflectivity and amplitude of cyclic variation) and wall thickness or systolic wall thickening was analyzed in the patients with HCM. A weak but significant correlation was found between the amplitude of cyclic variation and both the systolic wall thickening and the diastolic wall thickness (r=.37, P<.05 and r=-.29, P<.05, respectively). No correlation was observed between myocardial reflectivity and wall thickness or systolic wall thickening. In addition, the amplitude of cyclic variation and reflectivity did not differ between patients with or without outflow tract obstruction.
| Discussion |
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The characterization of HCM by ultrasonic backscatter analysis in adult patients has provided evidence of an increase in ultrasonic myocardial reflectivity10 both in the septum and in the posterior wall. A reduction of the cardiac cycledependent variation of the backscattered power has also been reported in both the septum and the posterior wall by some authors9 and only in the septum by others.8 Myocardial backscatter characteristics in children with HCM have not been reported. Therefore, we investigated the effect of age on backscatter parameters in patients with HCM and the effect of oral verapamil administration in children.
Like adult patients, children with HCM exhibit a reduction of the amplitude of cyclic variation of the power curve both in the septum and in the posterior wall. In the children, however, myocardial reflectivity was not significantly different from that in the normal control group and was significantly lower than in the adult patients with HCM. Therefore, in patients with HCM, ultrasonic myocardial reflectivity (as assessed by backscatter analysis) is normal at <10 years old but is significantly increased in adults.
The mechanisms that contribute to an increase in ultrasonic reflectivity of myocardial tissue in HCM are believed to be an increase in collagen content of the myocardium19 20 and the cellular disarray characteristic of this condition. Both factors are able to modify backscatter variables.21 22 23 24 Therefore, the greater myocardial reflectivity observed in adult patients can be related to an age-related increase in collagen content and/or to a greater degree of cellular disarray. The reported increase with age in myocardial collagen content in cardiomyopathic hamsters25 supports this hypothesis.
The reduction in the amplitude of the cyclic variation in the septum observed in our adult HCM patients is in agreement with previous results.8 9 The similar reduction in amplitude in the posterior wall is concordant with the results of some investigators9 but not with others.8 Although involvement of both septum and posterior wall is consistent with the findings that histological abnormalities are not confined to the hypertrophied segments of the heart,26 heterogeneous expression of the cardiomyopathic process might also explain normal backscatter properties in the posterior wall in some cases.8
The inotropic state of the myocardium27 28 and the presence of myocardial ischemia4 6 7 are factors that have been shown to reduce the amplitude of the backscatter cyclic variation. Since effort myocardial ischemia is a common feature of HCM patients,29 30 a reduction of the amplitude of cyclic variation might be expected during or shortly after exercise. At rest, however, myocardial ischemia should have less impact; therefore, other factors, such as the reduction of intrinsic myocardial contractility, may contribute to the reduction of amplitude observed in patients with HCM under resting conditions.
The weak but significant correlation between diastolic wall thickness and systolic wall thickening and the amplitude of the cyclic variation in patients with HCM is in accord with similar previous results4 5 6 7 8 and confirms that this backscatter index is only in part (given the weakness of the correlation) affected by these factors. Contrasting results obtained in isolated pig hearts have been explained by differences in the experimental model.31 A rough estimate of the contribution of wall thickening (or thickness) to the cyclic amplitude variation can be derived from the squared value of the correlation coefficients (
8% to 15%).
The efficacy of verapamil in the treatment of HCM has been related to the beneficial effects of the drug on oxygen consumption, myocardial contractility and relaxation, and possibly dilatation of small arteries. The absence of a significant difference in the ultrasonic data before and after verapamil administration in the children with HCM in this study is probably related, on the one hand, to the dependence of the myocardial ultrasonic reflectivity on anatomic structural elements that cannot be affected by drug administration and, on the other hand, to the fact that the intrinsic negative inotropic effect of the drug may be compensated by the positive effect on myocardial relaxation and vascular tone.
In conclusion, our data demonstrate that HCM patients <10 years old, reported to possess clinical and prognostic characteristics distinct from adult patients, exhibit normal ultrasonic myocardial reflectivity, in contrast to adults, in whom reflectivity is increased. This age-dependent variation of the echogenic structure of the myocardium is probably related to a greater myocardial collagen content and/or cellular disarray in the adult. These data indicate that ultrasonic tissue characterization provides unique information that may help define the presence and extent of myocardial structural abnormalities in a disease characterized by a heterogeneous clinical expression.32
Received March 13, 1996; revision received July 1, 1996; accepted July 5, 1996.
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