Ultrasonic tissue characterization of human hypertrophied hearts in vivo with cardiac cycle-dependent variation in integrated backscatter

Integrated ultrasonic backscatter (IB) is a noninvasive measure of the acoustic properties of myocardium. Previous experimental studies have indicated that altered acoustic properties of the myocardium are reflected by the magnitude of variation of IB during the cardiac cycle. In our study, cardiac cycle-dependent variation of IB was noninvasively measured using a quantitative IB imaging system in 12 patients with uncomplicated pressure-overload hypertrophy and 13 patients with hypertrophic cardiomyopathy. Sixteen normal subjects served as a control. The magnitude of cardiac cycle-dependent variation of IB for the posterior wall was 6.0 +/- 0.9 dB in normal subjects, 5.7 +/- 0.8 dB in the patients with uncomplicated pressure-overload hypertrophy, and 6.7 +/- 2.1 dB in the patients with hypertrophic cardiomyopathy. There were no significant differences among any of these groups. In contrast, the magnitude of cardiac cycle-dependent variation of IB for the septum was significantly smaller in the patients with uncomplicated pressure-overload hypertrophy (2.8 +/- 1.3 dB) and in the patients with hypertrophic cardiomyopathy (3.1 +/- 2.3 dB) than in normal subjects (4.9 +/- 1.0 dB). The magnitude of cardiac cycle-dependent variation of IB was smaller as the wall-thickness index increased (r = -0.53, p less than 0.01, n = 82 for all data). This IB measure also correlated with percent-systolic thickening of the myocardium (r = 0.67, p less than 0.01, n = 82). Thus, alteration in the magnitude of cardiac cycle-dependent variation of IB was observed in hypertrophic hearts and showed apparent regional myocardial differences.     

Ultrasonic tissue characterization with a real time integrated backscatter imaging system in normal and aging human hearts

Experimental studies have shown that variation in the magnitude of integrated ultrasonic backscatter during the cardiac cycle represents acoustic properties of myocardium that are affected by pathologic processes; however, there are few clinical studies using integrated backscatter. Forty subjects without cardiovascular disease (aged 22 to 71 years, mean 41) were studied with use of a new M-mode format integrated backscatter imaging system to characterize the range of cyclic variation of integrated backscatter in normal subjects. Cyclic variation in integrated backscatter was noted in both the septum and the posterior wall in all subjects. The magnitude of the cyclic variation of integrated backscatter and the interval from the onset of the QRS wave of the electrocardiogram to the minimal integrated backscatter value were measured using an area of interest of variable size for integrated backscatter sampling and a software resident in the ultrasound scanner. The magnitude of cyclic variation was larger for the posterior wall than for the septum (6.3 +/- 0.8 versus 4.9 +/- 1.3 dB, p less than 0.01). The interval to the minimal integrated backscatter value was 328 +/- 58 ms for the septum and 348 +/- 42 ms for the posterior wall (p = NS). There was a weak correlation between the magnitude of cyclic variation of integrated backscatter and subject age for the posterior wall (r = -0.47, p less than 0.01), but this was not significant for the septum (r = -0.21) (partially because of inability to exclude specular septal echoes) and septal endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial integrated ultrasonic backscatter in patients with dilated cardiomyopathy: prediction of response to beta-blocker therapy

BACKGROUND: Myocardial integrated backscatter (IB) imaging has been reported to be useful for ultrasonic tissue characterization and delineation of myocardial viability or fibrosis. beta-Blocker therapy has beneficial effects for patients with dilated cardiomyopathy (DCM), but there are no clear findings that indicate which patients with DCM will respond to this therapy. This study was performed to evaluate whether myocardial IB analysis can predict the response to beta-blocker therapy. METHODS AND RESULTS: We prospectively performed echocardiographic examination with IB analysis in 29 patients with DCM (20 men, 9 women) before starting bisoprolol therapy and in 15 normal subjects. Standard echocardiographic examination and IB analysis in the left ventricular wall in the 2-dimensional short-axis view were performed and the magnitude of cyclic variation (CV) of IB and calibrated myocardial IB intensity (subtracted pericardial) were obtained from the interventricular septum and the left ventricular posterior wall. Sixteen patients responded to bisoprolol therapy and 13 did not respond after 12 months of full-dose therapy. Calibrated myocardial IB intensity was lower in responders relative to nonresponders in both the interventricular septum (responders, -20.1 +/- 3.6 dB vs nonresponders, -9.8 +/- 5.1 dB, P <.0001; controls, -20.1 +/- 4.4 dB) and posterior wall (responders, -20.6 +/- 3.6 dB vs nonresponders, -14.6 +/- 4.2 dB, P =.0002; controls, -22.7 +/- 3.3 dB). Also, the lower the myocardial intensity in the interventricular septum or posterior wall, the better left ventricular systolic function improved after beta-blocker therapy. However, CV was lower in both DCM groups than in the controls, and CV in the interventricular septum was lower in nonresponders than in responders (responders, 4.0 +/- 4.1 dB vs nonresponders, -0.8 +/- 6. 1 dB, P <.02; controls, 8.3 +/- 2.4 dB). In addition, CV in the posterior wall showed no difference between the 2 DCM groups (responders, 5.6 +/- 1.3 dB vs nonresponders, 5.1 +/- 3.5 dB, P = not significant; controls, 9.6 +/- 2.5 dB). Also, the percent fibrosis on right ventricular endomyocardial biopsy specimens showed no distinctions between these 2 groups (responders, 25.1% +/- 16.1% vs nonresponders, 24.9% +/- 15.0%, P = not significant). CONCLUSIONS: These findings suggest that left ventricular myocardial IB data, especially IB intensity, provide useful information for predicting the response to beta-blocker therapy in patients with DCM. However, right ventricular endomyocardial biopsy findings do not appear to contribute to discriminating between the 2 groups.     

Ultrasonic myocardial tissue characterization in patients with hypertrophic cardiomyopathy and pressure-overloaded hypertrophy by backscattered energy temporal analysis.

This study measured integrated backscatter (IB) values in the subendocardium and subepicardium of patients with hypertrophy using the newly developed Backscattered Energy Temporal Analysis (BETA) system, and evaluated the differences of acoustic properties according to etiology. Twenty-one patients with hypertrophic cardiomyopathy (HCM), 16 with pressure-overloaded hypertrophy (POH), and 21 controls were studied. M-mode formatted IB images were obtained using BETA and the region of interest (ROI), automatically divided into epicardial and endocardial halves of the myocardium, was placed in the ventricular septum and posterior wall. Values for the cyclic variation of IB (CVIB) in the entire ROI and in each half of the ROI were obtained. CVIB significantly decreased in the ventricular septum in HCM and POH compared with normal subjects, but there were no significant differences between HCM and POH. In the posterior wall, the CVIB was less in the subendocardium than in the epicardium in POH, and was also less than in normal subjects (7.0+/-1.7 dB vs 8.6+/-1.9 dB and 8.8+/-2.1 dB, p<0.05, respectively). Separate ultrasonic tissue characterization of the subendocardium and subepicardium provides further etiological information of various heart diseases.     

Ultrasonic tissue characterization with integrated backscatter. Acute myocardial ischemia, reperfusion, and stunned myocardium in patients

We have previously shown in studies of experimental animals that myocardium exhibits a cardiac cycle-dependent variation of integrated backscatter that reflects regional myocardial contractile performance and that is blunted promptly after arterial occlusion and recovers after reperfusion. To define the clinical utility of ultrasonic tissue characterization with integrated backscatter for detection of acute myocardial infarction and reperfusion, 21 patients (14 men and seven women) were studied in the cardiac care unit within the first 24 hours (mean time, 11.3 hours; range, 3.5-23.8 hours) after the onset of symptoms indicative of acute myocardial infarction with conventional two-dimensional and M-mode echocardiography and with analysis of integrated backscatter. The magnitude of cyclic variation of integrated backscatter was measured from several sites within acute infarct regions and normal regions remote from the infarct zone for each patient. The average magnitude of cyclic variation among all patients (n = 21) was 4.8 +/- 0.5 dB in normal regions compared with 0.8 +/- 0.3 dB in infarct regions (p less than 0.05) within the first 24 hours after the onset of symptoms. Among the patients who had two studies, 15 (mean, 7.1 days; range, 2-31 days for second study) underwent coronary arteriography to define vessel patency. In patients with vessels with documented patency (n = 10), the magnitude of cyclic variation in infarct regions increased over time from 1.3 +/- 0.6 to 2.5 +/- 0.5 dB from the initial to final study (p less than 0.05). Patients with occluded infarct-related arteries (n = 5) exhibited no significant recovery of cyclic variation (0.3 +/- 0.3-0.6 +/- 0.3 dB). A blinded analysis of standard two-dimensional echocardiographic images revealed no significant recovery of wall thickening in either group over the same time intervals. Ultrasonic tissue characterization promptly detects acute myocardial infarction and may delineate potential beneficial effects of coronary artery reperfusion manifest by restoration of cyclic variation of integrated backscatter in the presence of severe wall motion abnormalities.     

Intramyocardial variability in integrated backscatter: effects of coronary occlusion and reperfusion

The present study was undertaken to characterize regional myocardial alterations of reflected ultrasound during the cardiac cycle in normal, ischemic, and postischemic reperfused myocardium. Time-averaged integrated backscatter (IB) and cardiac cycle-dependent amplitude modulation were measured from subepicardial, midmyocardial, and subendocardial regions of the left ventricular apex and the midportion of the right ventricular free wall under normal conditions (n = 5), after 1 hr of 100% acute left anterior descending (LAD) occlusion (n = 8), and after 15 min LAD occlusion plus 120 min reperfusion (n = 5) in anesthetized, ventilated open-chest dogs. A significant increase in time-averaged IB was observed in the subepicardium, the midmyocardium, and the subendocardium during ischemia and reperfusion, but there was no intramyocardial variability. Cardiac cycle-dependent amplitude modulation of IB was significantly higher in the normal subendocardium than in the subepicardium (4.3 +/- 0.6 vs 2.9 +/- 0.8 dB, p less than .01) and midmyocardium (2.8 +/- .05 dB, p less than .01). This transmural gradient in amplitude modulation was abolished during ischemia and reperfusion. We conclude that cardiac cycle-dependent amplitude modulation in IB has a transmural dependence in the normal myocardium and this is abolished during acute myocardial ischemia.     

Reproducibility of quantitative backscatter echocardiographic imaging in normal subjects.

Cyclic backscatter variation is useful in differentiating normal from ischemic and myopathic myocardium; however, there are few data on the reproducibility of clinical cyclic variation measurements. Therefore, a study using 2-dimensional and M-mode backscatter imaging was performed in 20 normal male subjects by 2 observers at an initial session and by 1 of the observers after 1 week. Cyclic variation on M-mode was calculated as the difference between the end-diastolic backscatter and the backscatter at the nadir. Two-dimensional determinations of backscatter were made using a single frame at end-diastole and one at end-systole. The cyclic change was the difference between backscatter measured in the end-diastolic and end-systolic frames. There were no statistically significant differences in analysis of variance among the grouped repeated measurements in either the interventricular septum or the posterior left ventricular wall. At the initial session, cyclic backscatter variation in the posterior wall using M-mode techniques was 5.9 +/- 1.8 dB (SD). The cyclic change in backscatter in the septal wall, using the 2-dimensional technique, was 4.3 +/- 2.4 dB. In the posterior wall, the cyclic change in backscatter was 5.7 +/- 1.7 dB. Pairwise observer correlations between repeated measurements ranged from -0.48 to 0.45. Thus, although there were no significant differences in group means on repeat measurements, repeated measurements in individual subjects were not reliably reproduced because of limited independent sampling of backscatter measurements at only 2 points in the heart cycle. Increased independent sampling and measurement from a backscatter waveform throughout the cardiac cycle may improve reproducibility of measurements.     

Early diastolic left ventricular function as a marker of acute cardiac rejection: a prospective serial echocardiographic study.

Changes in left ventricular early diastolic time intervals are sensitive indicators of incipient left ventricular dysfunction. We tested the hypothesis that acute rejection in cardiac transplant recipients is associated with alteration of early diastolic myocardial function, as expressed by the time interval Te, a parameter derived from digitized M-mode echocardiograms. Te is defined as the time interval between maximal posterior wall contraction and the point of peak posterior wall endocardium retraction velocity, as determined by the nadir of the computed first derivative curve. In transplant patients without rejection (group A, n = 48), Te was prolonged compared to healthy individuals (group C, n = 35) (79.0 +/- 12.5 ms vs 64.0 +/- 7.9 ms; p < 0.0001). During acute rejection (group B, n = 18) transplant patients had significantly longer mean Te values compared to transplant patients without rejection (group A) (97.8 +/- 17.9 ms vs 79.0 +/- 12.5 ms; p < 0.0001). Longitudinal studies in individual patients (group D, n = 18) demonstrated that rejection is associated with prolongation of Te (94.5 +/- 16.0 ms during rejection vs 79.0 +/- 10.3 ms before rejection; p < 0.0002) and that Te returns to individual baseline values in response to treatment (79.2 +/- 9.4 ms after therapy vs 79.0 +/- 10.3 ms before rejection; NS). In a prospective study, Te changes in transplant patients (group E, n = 96) were correlated with myocardial biopsy results. Sixty-one biopsies showed acute rejection, and 115 biopsies were negative.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sensitive detection of myocardial contraction abnormality in chronic hemodialysis patients by ultrasonic tissue characterization with integrated backscatter

Since acoustic properties of the myocardium are sensitive to the myocardial structure and the contractile conditions of myocyte, the authors evaluated cardiac dysfunction based on the integrated ultrasonic backscatter in 18 hemodialysis (HD) patients (duration: 102 +/- 84 months, mean age: 57.6 +/- 9.7 years) and 11 age-matched normals. The cyclic variation of integrated backscatter (CV-IB) at interventricular septum (IVS) and left ventricular posterior wall (PW) was measured and compared with percent fractional shortening (%FS) and percent wall thickening (%Th). The CV-IB of HD patients was smaller than that of control subjects (IVS: 6.2 +/- 1.1 dB vs 8.2 +/- 1.1 dB, p = 0.0003 and PW: 8.4 +/- 2.2 vs 10.3 +/- 1.3, p= 0.025). No significant difference was observed in %FS and %Th between HD patients and control subjects. In HD, the ratio of velocities of early diastolic inflow (E) to late atrial inflow was decreased (0.7 +/- 0.2 vs 1.1 +/- 0.7, p = 0.049) and deceleration time of E was prolonged significantly (200 +/- 28 msec vs 159 +/- 30 msec, p = 0.0082). In the absence of overt cardiac systolic dysfunction, myocardial damage indicated as a decrease in CV-IB and diastolic dysfunction identified on transmitral velocity waveform were detected, which may reflect from the myocardial fibrosis. As a mechanism, pressure overload, hyperparathyroidism, and anemia were neglected, and the other humoral factors may contribute to the myocardial damage in chronic renal failure.     

Abnormal myocardial acoustic properties in diabetic patients and their correlation with the severity of disease.

Although patients with diabetes mellitus may be afflicted by cardiomyopathy, its prevalence and nature are controversial. Studies have shown that fibrosis alters the acoustic properties of the heart in animals and humans and that the changes are detectable by cardiac tissue characterization with ultrasound. The present study was performed to characterize myocardial acoustic properties in patients with insulin-dependent diabetes to determine whether ultrasound tissue characterization could detect changes potentially indicative of occult cardiomyopathy. The magnitude of cyclic variation of myocardial ultrasound integrated backscatter and its phase delay with respect to the onset of the cardiac cycle in the septum and posterior wall of the left ventricle were measured in 54 patients with diabetes who had no overt cardiac disease. Conventional echocardiography documented normal ventricular systolic function in 96%. As compared with results in age-matched patients without diabetes studied previously, cyclic variation of integrated backscatter was reduced (4.6 +/- 0.8 vs. 3.6 +/- 1.4 dB; p less than 0.001). In addition, delay was significantly increased (0.86 +/- 0.09 vs. 0.99 +/- 0.15). The primary analysis of the data focused on differences among the diabetic patients. Reduction of cyclic variation of backscatter was greatest in patients with diabetes who had neuropathy (3.2 +/- 1.0 dB; p less than 0.001) as was the increase in delay (1.04 +/- 0.16, p less than 0.001 vs. values in patients without neuropathy). Retinopathy and nephropathy were associated with abnormal myocardial acoustic properties as well. Thus, abnormalities that may reflect fibrosis or other occult cardiomyopathic changes in diabetic patients without overt heart disease are readily detectable by myocardial tissue characterization with ultrasound and parallel the severity of noncardiac diabetic complications.     

Recent experience with ultrasonic tissue characterization

The current effort in the research laboratory at Stanford University Medical Center attempts tissue characterization using the parameter of cyclic variation of integrated ultrasonic backscatter (CVIBS). This parameter is available using prototype equipment that concentrates on the relative change in ultrasonic backscatter rather than the absolute level of backscatter measured. The interobserver reproducibility is quite good. The magnitude of CVIBS is greater in the posterior wall than in the septum generally. There is a weak association of aging with the magnitude of CVIBS. Measurement of CVIBS in patients with uncomplicated pressure overload hypertrophy and those with hypertrophic cardiomyopathy shows values in the posterior wall to be similar for all groups; however, the values for the septum were significantly smaller in patients in both hypertrophy groups compared with normal subjects. Studies in human cardiac allografts for the recognition of acute rejection have been carried out using CVIBS. A decrease in the magnitude of this parameter during rejection, compared to the baseline level, was characteristically seen. Return to prerejection levels was not invariably seen. Among the different systems for ultrasonic tissue characterization, the current system using CVIBS has been successful in specific studies.     

Immunoexpression of perforin and granzyme B on infiltrating lymphocytes in human renal acute allograft rejection

Graft destruction can be effected by direct cell-to-cell contact between activated effector T cell and a target graft resulting in delivery of cytotoxic molecules. Perforin and granzyme B can be used as activation markers for cytotoxic cells in allograft tissue. The aim of the study was to determine the immunoexpression of perforin and granzyme B by immune cells infiltrating renal tissue during acute allograft rejection and to evaluate any correlation between the phenotype of infiltrating lymphocytes and cells expressing cytotoxic granules as well as the severity of graft damage as defined by Banff 97 criteria. Immunoperoxidase staining was carried out using monoclonal antibodies anti-perforin, -granzyme B, -CD3 and -CD8 on renal allograft biopsy specimens from twenty one patients with acute renal transplant rejection: Banff 97 IA (n = 11) and Banff 97 IB (n = 10). As a control 11 biopsy specimens of renal transplant patient without any signs of rejection were used. All allograft biopsy specimens with acute renal transplant rejection contained a high number of CD3+ T cells (Banff IA: 437.4 +/- 154.4 and Banff IB: 825 +/- 339.9 vs 123.4 +/- 52.5 in controls) and CD8+ T lymphocytes (Banff 97 IA: 177.6 +/- 89.2 and Banff IB: 293.2 +/- 112.4 vs 64.2 +/- 37.1 in controls). Immunostaining for granzyme B and perforin was negative in controls. The immunopositivity for perforin was similar in Banff IA and Banff IB acute allograft rejection (1.5 +/- 0.6 vs 1.8 +/- 0.8, respectively). Granzyme B+ cell count was significantly higher in severe rejection group Banff IB (128.3 +/- 74.3) than in Banff IA group (48.2 +/- 18.3). Moreover, in acute allograft rejection Banff IB the number of granzyme B+ cells and perforin+ cells was correlated with the number of CD8+ T cells. In conclusion, our results suggest that in acute tubulointerstitial allograft rejection activated cytotoxic T lymphocytes play a major role. The strong immunopositivity for granzyme B on infiltrating cells in renal transplant tissue is suggested as a marker of severity of graft damage.     

Myocardial ischemic-fibrotic injury after human heart transplantation is associated with increased progression of vasculopathy, decreased cellular rejection and poor long-term outcome

OBJECTIVES: We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute cellular rejection and long-term outcome. BACKGROUND: Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. METHODS: One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for cellular rejection, vascular rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. RESULTS: Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of cellular rejection (1.7 +/- 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 +/- 0.28 mm, p < 0.0001) and poor seven-year event-free survival (49%, p = 0.01). CONCLUSIONS: The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute cellular rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.     

Early detection of doxorubicin-induced myocardial damage by ultrasound tissue characterization with integrated backscatter.

Doxorubicin (DXR) is one of the most effective antineoplastic agents, but its use is limited by its myocardial toxicity. Myocardial injury reduces the cyclic variation of integrated backscatter (CV-IBS) and so the present study was designed to investigate whether CV-IBS can be used to detect the early phase of myocardial damage in patients receiving DXR. Thirty-four subjects constituted the study population, none of whom showed clinically evident heart failure. CV-IBS was obtained for both the interventricular septum and the left ventricular posterior wall in the parasternal short-axis view. Standard echographic measures of left ventricular function were also made. Subjects without DXR exposure or evident cardiac diseases served as controls. The total dose of DXR administered per patient was 339+/-164 mg/m2 (range: 95-680 mg/m2). Conventional echographic parameters, including left ventricular wall thickness, dimensions, fractional shortening, and ejection fraction, showed no significant differences between the 2 groups. In contrast, CV-IBS was significantly decreased in the DXR group compared with the control group (septum: 4.7+/-1.7 vs 7.2+/-1.9 dB, p<0.0001; posterior wall: 6.7 +/-2.2 vs 8.0+/-1.6 dB, p<0.05). CV-IBS can be used as an early indicator of DXR-induced myocardial damage in patients demonstrating normal left ventricular systolic function.     

Detection of cardiac sarcoidosis using cardiac markers and myocardial integrated backscatter

BACKGROUNDS: It is not known whether cardiac markers and cyclic variations of integrated backscatter can be used to detect cardiac sarcoidosis. METHODS: We studied 62 patients with sarcoidosis affecting the lung, eyes, skin, or heart (27 patients with cardiac involvement and 35 patients without). The cyclic variation of integrated backscatter and wall thickening was evaluated in the left ventricular anterior septum and posterior wall. Plasma A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) concentrations and serum cardiac troponin T were also determined. RESULTS: Plasma natriuretic peptide concentrations were higher in the cardiac involvement group (ANP: 15.5 [interquartile range (IQR) 2.5-34.0] vs. 12.0 [10.0-16.5] pg/ml, P=0.25; BNP: 28.6 [5.9-141] vs. 10.1 [4.8-15.4] pg/ml, P=0.049). However, cardiac troponin T concentration was <0.01 ng/ml in all patients. Receiver-operator characteristic (ROC) analysis showed that both ANP and BNP could identify patients with high-degree atrioventricular block, ventricular tachyarrhythmias, or symptomatic heart failure (the areas under the ROC curve were 0.94 and 0.97, respectively). The cardiac involvement group could be distinguished from the noninvolvement group by combining cutoff values for the magnitude of integrated backscatter cyclic variation (5.5 dB) and wall thickening (30%), albeit only for the posterior wall. CONCLUSION: Both ANP and BNP are useful markers for identifying patients with sarcoidosis and cardiac complication(s). Moreover, evaluation of integrated backscatter cyclic variation combined with wall thickening may be of help in detecting cardiac involvement in the posterior wall.     

Prognostic implications derived from ultrasonic tissue characterization with myocardial integrated backscatter in patients with dilated cardiomyopathy

BACKGROUND: Various clinical parameters have been reported to predict survival in patients with dilated cardiomyopathy (DCM). Myocardial ultrasonic integrated backscatter (IB) imaging has a potential to perform in vivo tissue characterization. The present study was performed to examine whether myocardial IB analysis can predict the prognosis of DCM patients. METHODS AND RESULTS: We prospectively carried out echocardiographic examinations with IB analysis in 43 patients with DCM (31 males, 12 females) under the standard treatment. IB analysis was performed in the left ventricular wall and the calibrated (subtracting pericardial data) myocardial IB intensity (IBI) was obtained from the interventricular septum and the left ventricular posterior wall. After the follow-up (8-39 months), 31 followed a good clinical course, but eight had cardiac death, one had partial left ventriculectomy for uncontrolled heart failure and three were hospitalized for worsening heart failure. Beta-blocker responded in 27 (87%) of the 31 with good clinical course, but it did not respond in 11 among the 12 with poor course. In these 12 DCM, left ventricular fractional shortening (LVFS) was lower (good: 18+/-5%, poor: 14+/-4, P<0.03) and calibrated IBI was higher in both the septum (good: -16.4+/-5.6 dB, poor: -11.1+/-4.2 dB, P<0.006) and the posterior wall (good: -19.5+/-3.6 dB, poor: -13.8+/-5.6 dB, P<0.004). On the Cox proportional hazard model analysis, only calibrated IBI in the septum >-17 dB, the cut-off score of calibrated IBI discriminating non-responders to beta-blocker therapy in our previous report, was related to the poor outcome (chi(2)=4.43, P=0.035). The stepwise multivariate analysis revealed that both calibrated IBI in the septum>-17 dB (chi(2)=4.43, P=0.035) and LVFS<15% (chi(2)=3.89, P=0.049) were useful to predict the poor clinical outcome. The event free rate assessed by the Kaplan-Meier method was also significantly reduced in patients with calibrated IBI in the septum >-17 dB (chi(2)=6.594, P=0.01) and calibrated IBI in the posterior wall>-17 dB (chi(2)=4.215, P=0.04). However, LVFS<15% (chi(2)=3.576, not significant) did not contribute to discriminating the event free rate in the clinical course. CONCLUSIONS: The present study demonstrated that myocardial IB intensity was higher in DCM patients who followed a poor clinical course rather than in those with a good outcome. Therefore, it is clarified that myocardial ultrasonic tissue characterization in DCM patients is useful for assessing their clinical outcome after receiving not only the standard treatment but also beta-blocker therapy.     

Quantitative assessment of ultrasonic myocardial reflectivity in hypertrophic cardiomyopathy

The purpose of this study was to investigate the relation between acoustic properties of the myocardium and magnitude of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy. An on-line radio frequency analysis system was used to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior free wall in 25 patients with hypertrophic cardiomyopathy and 25 normal age-matched control subjects. The integrated values of the radio frequency signal were normalized for the pericardial interface and expressed in percent. Tissue reflectivity was significantly increased in the hypertrophied ventricular septum, as well as in the nonhypertrophied posterior free wall, in patients with hypertrophic cardiomyopathy (58 +/- 15% and 37 +/- 12%, respectively) compared with values in normal subjects (33 +/- 10% and 18 +/- 5%, respectively; p less than 0.001). Furthermore, measurements of reflectivity of the septum or posterior free wall, or both, were beyond 2 SD of normal values in greater than 90% of the patients and were also abnormal in each of the five study patients who had only mild and localized left ventricular hypertrophy. No correlation was identified between myocardial tissue reflectivity and left ventricular wall thickness in the patients with hypertrophic cardiomyopathy (correlation coefficient r = 0.4; p = NS). These findings demonstrate that myocardial reflectivity is abnormal in most patients with hypertrophic cardiomyopathy and is largely independent of the magnitude of left ventricular hypertrophy. Moreover, quantitative analysis of ultrasonic reflectivity can differentiate patients with hypertrophic cardiomyopathy from normal subjects independently of clinical features and conventional echocardiographic measurements.     

Deficient acceleration of left ventricular relaxation during exercise after heart transplantation.

BACKGROUND. The exercise-induced rise in left ventricular filling pressures after cardiac transplantation is considered to be the result of a blunted heart rate response, of elevated venous return, and of unfavorable passive late-diastolic properties of the cardiac allograft. In contrast to passive late-diastolic left ventricular properties, the effect of left ventricular relaxation on the exercise-induced rise in left ventricular filling pressures of the cardiac allograft has not yet been studied. In the present study, the response of left ventricular relaxation to exercise was investigated in transplant recipients and compared with left ventricular relaxation observed in normal control subjects exercised to the same heart rate. Moreover, the response of left ventricular relaxation of the cardiac allograft to beta-adrenoreceptor stimulation, to reduced left ventricular afterload, and to increased myocardial activator calcium was investigated by infusion of dobutamine and of nitroprusside and by postextrasystolic potentiation. METHODS AND RESULTS. Twenty-seven transplant recipients were studied 1 year (n = 17), 2 years (n = 7), 3 years (n = 2), and 4 years (n = 1) after transplantation. All patients were free of rejection and of significant graft atherosclerosis at the time of study. Tip-micromanometer left ventricular pressure recordings and cardiac hemodynamics were obtained at rest, during supine bicycle exercise stress testing (n = 27), during dobutamine infusion at a heart rate matching the heart rate at peak exercise (n = 8), during nitroprusside infusion (n = 9), and after postextrasystolic potentiation (n = 10). Tip-micromanometer left ventricular pressure recordings were also obtained in a normal control group (n = 9) at rest and during supine bicycle exercise stress testing to a heart rate, which matched the heart rate of the transplant recipient group at peak exercise. Left ventricular relaxation rate was measured by calculation of a time constant of left ventricular pressure decay (T) derived from an exponential curve fit to the digitized tip-micromanometer left ventricular pressure signal. In the transplant recipients, exercise abbreviated T from 43 +/- 6 to 40 +/- 8 msec (p less than 0.01) and caused a rise of left ventricular minimum diastolic pressure (LVMDP) from 5 +/- 2 to 9 +/- 6 mm Hg (p less than 0.001). In normal control subjects, exercise induced a 2.5 times larger abbreviation of T (from 42 +/- 7 to 34 +/- 6 msec; p less than 0.001) and a small drop in LVMDP from 5 +/- 2 to 4 +/- 3 mm Hg (p less than 0.05). In the transplant recipients, the change in T (delta T) from rest to exercise was variable ranging from an abbreviation, as observed in normal controls, to a prolongation and was significantly correlated with the change in RR interval (delta RR) and the change in left ventricular end-diastolic pressure (delta LVEDP) (delta T = 0.068 delta RR + 0.58 delta LVEDP-2.2; r = 0.76; p less than 0.001). In a first subset of transplant recipients (n = 8), dobutamine infusion resulted in a heart rate equal to the heart rate at peak exercise, a left ventricular end-diastolic pressure (8 +/- 7 mm Hg) lower than at peak exercise (22 +/- 6 mm Hg; p less than 0.05) and a T value (32 +/- 9 msec), which was shorter than both resting value (44 +/- 5 msec; p less than 0.005) and value observed at peak exercise (40 +/- 8 msec; p less than 0.01). In a second subset of transplant recipients (n = 9), nitroprusside infusion and postextrasystolic potentiation resulted in a significant prolongation of T from 41 +/- 7 to 56 +/- 10 msec (p less than 0.05) and a characteristic negative dP/dt upstroke pattern with downward convexity as previously observed in left ventricular hypertrophy. CONCLUSIONS. Exercise after cardiac transplantation resulted in a smaller acceleration of left ventricular relaxation than in a normal control group exercised to the same heart rate...     

Age-associated decline in cardiac allograft rejection

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.     

The potential clinical role of ultrasonic strain and strain rate imaging in diagnosing acute rejection after heart transplantation.

BACKGROUND: There has been a continued search for a more sensitive noninvasive technique for detecting sub-clinical acute rejection in heart transplant recipients. Ultrasonic deformation imaging (strain/strain rate) is sensitive in detecting sub-clinical abnormalities in regional systolic function and could potentially be sufficiently sensitive to detect changes in deformation induced by graft rejection. AIM: To assess the use of strain (S) and strain rate (SR) imaging as a noninvasive method for monitoring and diagnosing acute rejection in heart transplant recipients. METHODS AND RESULTS: A prospective preliminary study was carried out involving 31 consecutive heart transplant patients who underwent a total of 106 routine follow up endomyocardial biopsy with correlative cardiac ultrasound data. To assess regional longitudinal deformation, ultrasonic S and SR data were acquired from the intraventricular septum, left ventricular (LV) lateral and right ventricular free walls (RVFW). For radial deformation, data were obtained from the LV posterior wall (LVPW). According to the International Society of Heart and Lung Transplantation criteria, 88 biopsies (Group 1) had grade 0 or IA rejection, and 18 biopsies (Group 2) had > or =grade IB rejection. Longitudinal peak systolic S and SR were decreased (p<0.05) in Group 2, compared to Group 1 in the RVFW basal and apical segments and the basal and mid segments of the LV lateral wall. Radial peak systolic S and SR were significantly lower (p<0.001) in Group 2, compared to Group 1. CONCLUSIONS: S/SR imaging might be a good technique and an additional tool for detecting > or =IB grade of acute rejection. The myocardial deformation, as assessed by S/SR imaging could be of clinical value in monitoring and diagnosing acute rejection in heart transplant recipients and could improve patients' management by reducing the number of biopsies performed.