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.     

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

BACKGROUND AND AIMS: It has been proven that a disturbance in angiogenesis contributes to the progression of myocardial interstitial fibrosis in idiopathic dilated cardiomyopathy (DCM). This study was designed to evaluate the relationship between serum activity of angiogenic factors and myocardial ultrasonic tissue characterization in patients with DCM. METHODS AND RESULTS: We studied 30 patients with DCM and 15 healthy control subjects. Serum levels of vascular endothelial growth factor (VEGF), interleukin (IL)-4 and IL-13 were measured using enzyme-linked immunosorbent assay. We determined calibrated myocardial integrated backscatter (IB) as the value of myocardial interstitial fibrosis using ultrasonic tissue characterization and also quantified the magnitude of cyclic variations in IB (CV-IB). Serum levels of VEGF and IL-13 were significantly higher in patients with DCM than in control subjects (both P<0.05). Calibrated IB was significantly higher and CV-IB was markedly lower in patients with DCM than in control subjects (both P<0.01). In patients with DCM, the levels of IL-13 significantly correlated with calibrated IB (r=0.520, P=0.018). In addition, there was a significant negative correlation between levels of VEGF and CV-IB (r=-0.611, P=0.007). CONCLUSION: The increase in serum VEGF and IL-13 may be closely related to alterations in myocardial texture in DCM.     

Serial measurement of integrated ultrasonic backscatter in human cardiac allografts for the recognition of acute rejection

Cyclic variation of integrated ultrasonic backscatter (IB) was noninvasively measured in the septum and left ventricular posterior wall using a quantitative IB imaging system to assess the alterations in the acoustic properties of myocardium associated with acute cardiac allograft rejection. The study population consisted of 23 cardiac allograft recipients and 18 normal subjects. In each cardiac allograft recipient, one to eight (mean, four) IB studies were performed, each within 24 hours of right ventricular endomyocardial biopsy performed for rejection surveillance. The magnitude of the cyclic variation of IB in the posterior wall was 5.9 +/- 0.9 dB in normal subjects and 6.2 +/- 1.3 dB in the cardiac allograft recipients without previous or current histological evidence of acute rejection (n = 17, p = NS vs. normal subjects). The magnitude of cyclic variation of IB in the septum was 4.8 +/- 1.1 dB in normal subjects and 3.8 +/- 2.0 dB in the cardiac allograft recipients (n = 15, p = NS vs. normal subjects). A significant decrease in the septal IB measure was observed in cardiac allograft recipients with left ventricular hypertrophy (wall thickness of at least 13 mm) (2.6 +/- 1.7 dB, n = 8, p less than 0.05 vs. normal subjects). IB studies were done before and during moderate acute rejection in 11 recipients (14 episodes). During moderate acute cardiac rejection, the magnitude of the cyclic variation in IB decreased from 6.7 +/- 1.3 to 5.1 +/- 1.4 dB in the posterior wall (n = 14, p less than 0.05) and from 4.2 +/- 2.1 dB to 2.9 +/- 1.8 dB in the septum (n = 12, p less than 0.05). These data suggest 1) the magnitude of the cyclic variation in IB of the septum is different in cardiac allografts with cardiac hypertrophy and normal subjects, possibly reflecting regionally depressed myocardial contractile performance and 2) acute cardiac rejection in humans is accompanied by an alteration in the acoustic properties of the myocardium. This change is detectable by serial measurement of the magnitude of the cyclic variation in IB, both in the septum and in the posterior wall.     

The influence of growth hormone therapy on ultrasound myocardial tissue characterization in patients with childhood onset GH deficiency

BACKGROUND: In growth hormone deficiency (GHD), a reduction in left ventricular mass (LV-mass) and impairment of systolic function has been shown. In this study, we investigated the effects of 12 months of GH replacement therapy on cardiac structure and functional indices measured by echocardiographic techniques in adult patients with childhood onset GH deficiency. METHODS: Sixteen patients (age 42.3+/-13.1 years, 10 males) were investigated before and after 12 months of GH treatment at a dose of 0.02 IU/kg/day (7 microg/kg/day). Echocardiography was performed including the ultrasound myocardial tissue characterization technique. We measured two parameters of the ultrasonic tissue characterization with integrated backscatter: the magnitude of the cardiac-cycle-dependent variation in integrated backscatter signals (CV-IBS) and the mean value of integrated backscatter signals calibrated by the pericardium (cal-IBS). RESULTS: Left ventricular diameter and wall thickness did not change after GH treatment, although systolic increase in interventricular septum thickness (IVS%) and systolic increase in posterior wall thickness (PWT%) increased significantly (IVS% 52.2+/-31.9% vs. 67.3+/-30.4% and PWT% 48.7+/-20.2% vs. 58.0+/-17.7%, p<0.01 and p<0.01, respectively). Ejection fraction increased from 56.2+/-7.2% to 63.2+/-6.1% (p<0.01). LV-mass index did not change after GH treatment (78.4+/-22.1 vs. 81.9+/-21.1 g/m(2)). CV-IBS increased significantly after GH treatment (p<0.05), in both the interventricular septum and the left ventricular posterior wall (4.7+/-1.5 vs. 5.8+/-1.9 dB for the interventricular septum, 4.9+/-1.8 vs. 6.5+/-2.4 dB for the left ventricular posterior wall, p<0.05 and p<0.05, respectively). Cal-IBS also increased significantly after GH treatment (-23.5+/-4.1 vs.-21.8+/-4.2 dB for the interventricular septum, -23.0+/-4.4 vs. -21.8+/-4.3 dB for the left ventricular posterior wall, p<0.01 and p<0.05, respectively). CONCLUSION: Twelve months GH treatment in adults with childhood onset GHD resulted in improvement of cardiac contractile performance. Observed changes in cal-IBS and CV-IBS suggest that GH treatment in this patient group can lead to a further somatic maturation of the heart, probably not accomplished previously.     

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.     

Impact of pulmonary regurgitation and age at surgical repair on textural and functional right ventricular myocardial properties in patients with tetralogy of Fallot.

BACKGROUND: The aim of this study was to identify non-invasively the potential impact of pulmonary regurgitation and age at surgical repair on the right ventricular (RV) textural and functional myocardial properties in patients operated on for tetralogy of Fallot (TOF). METHODS: We assessed the average intensity (Int.(1B)) and the cyclic variation (CV(IB)) of the echocardiographic backscatter curve in 30 TOF patients (mean age 16.2 +/- 8.3 years), who had undergone corrective surgery (mean age at repair 3.2 +/- 2.6 years, range 0.2-11 years). They were divided into three age- and body surface area (BSA)-matched subgroups according to the results of the surgical repair: 12 patients had no significant postsurgical sequelae (group I), 12 patients had isolated moderate-severe pulmonary regurgitation (group II), and 6 patients had pulmonary regurgitation associated with significant (> 30 mmHg) RV outflow tract obstruction (group III). In addition, 30 age-, sex- and BSA-matched normal subjects were identified as the control group. RESULTS: In our study population, CV(IB) was lower (7.86 +/- 2.5 vs 10.6 +/- 1.4 dB, p < 0.001) and Int.IB higher (-18.6 +/- 4.1 vs -21 +/- 2.8 dB, p = 0.01) compared to the control group. Comparison between the control group and each subgroup of TOF patients showed: a) comparable values of CV(IB) and Int.(IB) in group I (10.6 +/- 1.4 vs 9.4 +/- 2.3 dB, p = 0.07; and -21 +/- 2.8 vs -21.4 +/- 2.3 dB, p = 0.7, respectively); b) Int.(IB) was significantly different only in group III (-21 +/- 2.8 vs -13.3 +/- 4.6 dB, p < 0.0001), c) CV(IB) was different either in group II or III (10.6 +/- 1.4 vs 7.42 +/- 2, p < 0.001; and 10.6 +/- 1.4 vs 5.56 +/- 1.8, p < 0.001, respectively). In addition, comparison of integrated backscatter indexes among the TOF subgroups revealed significant differences of CV(IB) between group I and II (9.4 +/- 2.4 vs 7.4 +/- 2, p = 0.03) and between group I and III (9.4 +/- 2.4 vs 5.56 +/- 1.8, p = 0.004), and of Int.(IB) between group I and III (-21.4 +/- 2.3 vs -13.3 +/- 4.66, p < 0.001) and between group II and III (-21.4 +/- 2.3 vs -18.6 +/- 2.8, p = 0.006). Group III patients, who had the most significant RV dilation, expressed as the ratio between RV and left ventricular end-diastolic diameter (0.55 +/- 0.8) compared to group II (0.67 +/- 0.11, p = 0.038) and group I (0.55 +/- 0.87, p < 0.001), showed the lowest values of CV(IB) (5.56 +/- 1.8 dB) and the highest values of Int.(IB) (-13.3 +/- 4.6 dB) Finally, in our study population, both the degree of RV dilation and the age at surgical repair significantly correlated with Int.(IB) (r = 0.49 and r = 0.4, p = 0.06 and p = 0.033, respectively) and inversely correlated with CV(IB) (r = -0.55 and r = -0.53, p = 0.002 and p = 0.003, respectively). CONCLUSIONS: In patients operated on for TOF: a) integrated backscatter analysis may identify patients with significant RV myocardial abnormalities related to postsurgical sequelae; b) residual pulmonary regurgitation, particularly if associated with pulmonary stenosis, appears to affect RV myocardial properties; c) an earlier repair of TOF may result in better preservation of myocardial characteristics.     

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.     

Tribble 3在糖尿病心肌病心肌间质重构时的表达和缬沙坦干预的影响

目的探讨Tribble3(TRB3)基因在大鼠Ⅱ型糖尿病心肌病心肌间质重构中的可能作用及缬沙坦干预的影响。方法32只Wistar大鼠以高脂高热量饮食诱导加小剂量链脲佐菌素注射建立Ⅱ型糖尿病心肌病动物模型,随机分为糖尿病心肌病组和缬沙坦治疗组(缬沙坦30mg·kg-1·d-1灌胃),以8只正常大鼠作对照。采用Masson染色测定心肌胶原含量,实时定量逆转录-聚合酶链反应检测心肌TRB3mRNA表达。结果与对照组比较,糖尿病心肌病组左室心肌组织胶原含量显著高(11·01±3·05比16·92±3·18,P<0·01),与糖尿病心肌病组相比,缬沙坦组心肌胶原含量明显低(16·92±3·18比13·23±3·14,P<0·05),心肌组织胶原含量与空腹血糖呈明显正相关(r=0·746,P<0·01);与对照组相比,糖尿病心肌病组大鼠心肌TRB3mRNA表达水平明显高(0·0198±0·0082比0·1108±0·0933,P<0·05);与糖尿病心肌病组比较,缬沙坦组TRB3mRNA表达水平明显低(0·1108±0·0933比0·0367±0·0234,P<0·05);与对照组比较,缬沙坦组TRB3mRNA表达水平差异无统计学意义(P>0·05);糖尿病心肌病组大鼠心肌TRB3mRNA表达与血糖正相关(r=0·69,P<0·05),与心肌组织胶原含量正相关(r=0·67,P<0·05)。结论首次证实TRB3基因在大鼠心肌中表达,发现了TRB3基因可能参与了糖尿病心肌病心肌间质重构,缬沙坦干预减轻糖尿病心肌病心肌间质重构,改善左室舒张和收缩功能,下调TRB基因的表达。     

Prognostic relevance of left ventricular diastolic function parameters in dilated cardiomyopathy

Patients with dilated cardiomyopathy (DCM) generally have an impaired functional capacity and poor long-term out-comes. A mortality of 5-15% per year has been described actually. Aim of this study was to verify the prognostic relevance of invasive and non-invasive parameters of diastolic function in patients with DCM. In 33 patients with DCM, cardiac catheterization was performed and left ventricular systolic (ejection fraction (EF; %)); left ventricular enddiastolic pressure (LVEDP; mmHg) and diastolic function (time constant of relaxation (T, ms); the constant of myocardial stiffness (b) were derived from biplane laevocardiography and simultaneous micromanometric registration of pressure-volume curves. For evaluation of clinical out-come, the follow-up period was defined as beginning on the day after cardiac catheterization and ending on the most recent date or with a cardiac event (death or cardiac transplantation). All patients were reevaluated for NYHA functional class and completed a standard questionnaire. The following hemodynamic parameters were evaluated: invasive parameters of left ventricular diastolic function (constant of relaxation: tau (ms), constant of myocardial stiffness: b)), as well as parameters of systolic function (ejection fraction (EF; %)), left ventricular pressure (LVEDP; mmHg), left ventricular muscle mass index (LVMMI; g/m2), left ventricular enddiastolic volume index (LVEDVI; ml/m2) and non-invasive parameters of morphological data, left ventricular systolic (fractional shortening (FS, %) and ejection fraction) and diastolic parameters with echocardiography. During the follow-up period of 36 months, 11 of 33 patients experienced a major cardiac event (cardiac death n = 8, heart transplantation n = 3). The major cause of death was progressive pump failure. The remaining 22 patients were further classified with respect to changes in functional status. While clinical symptoms could be improved medically in patients with moderate increase of myocardial stiffness, patients with severe increase of myocardial stiffness (b: 76.1 +/- 12.1 vs 17.9 +/- +8.1, p < 0.001) could not be improved and suffered more cardiac events. Doppler echocardiographic measurements in these patients showed a restrictive filling pattern (VE 0.91 +/- 0.21 vs 0.64 +/- 0.18 m/s; p < 0.01; VA 0.52 +/- 0.23 vs 0.57 +/- 0.24 m/s; p < 0.01, deceleration time 129 +/- 17 vs 211 +/- 14 ms; p < 0.01). The medical heart failure therapy was comparable in both groups. In patients with cardiac events, the diastolic left ventricular variables did not significantly differ between patients who underwent heart transplantation and those who died. Patients who demonstrated a sole impairment of relaxation (tau: > 50 ms) suffered no cardiac events. Impaired diastolic function contributes to the clinical picture of congestive heart failure. Parameters of left ventricular diastolic function are powerful and important predictors of major cardiac events in patients with DCM, like heart transplantation and non-sudden death, and may indicate future clinical success of medical treatment. Invasive and non-invasive parameters of diastolic function reveal comparable information for the estimation of prognosis of patients with DCM in order to initiate early therapy.     

Echocardiographic prediction of clinical outcome in medically treated patients with aortic stenosis

BACKGROUND: The onset of symptoms is crucial in the natural history of severe aortic stenosis. In contrast, the impact of the degree of valve obstruction and left ventricular dysfunction on clinical outcome in terms of progression of symptoms and mortality is undefined. METHODS AND RESULTS: Between April 1989 and June 1996, 108 patients (75% male, aged 68.7 +/- 10.3 years) with pure and isolated aortic stenosis of at least moderate degree had a complete Doppler echocardiography. Left ventricular end-diastolic and end-systolic diameters, thickness of ventricular septum, mass and ejection fraction, and maximal instantaneous aortic gradient were measured. Patients were followed up through March 1999. Sixty-five patients who underwent aortic valve replacement were censored at the time of surgery. The end point was considered to be death or symptomatic progression (onset of new symptoms or worsening of symptoms). At the time of diagnosis 64 (59%) were in New York Heart Association (NYHA) class I-II and 44 (41%) in NYHA class III-IV. After a mean follow-up of 46 +/- 21 months 6 patients died and 45 had worsening of symptoms. Univariate predictors of clinical outcome (death and worsening of symptoms) included left ventricular end-diastolic diameter (hazard ratio 1.03, P =.08), left ventricular end-systolic diameter (HR 1.04, P =.012), and left ventricular septum thickness (HR 1.14, P =.009) but not the degree of aortic obstruction. Multivariate predictors of clinical outcome were left ventricular septum thickness (P =.016) and left ventricular end-systolic diameter (P =.008). CONCLUSION: In patients with various degrees of aortic stenosis the rate of clinical outcome is predicted by left ventricular function and septum thickness. Therefore both the left ventricular and aortic valve gradients should be taken into account when choosing the timing of intervention.     

C-Reactive protein in dilated cardiomyopathy.

The prognosis for patients with idiopathic dilated cardiomyopathy (DCM) is poor, although clinical features are variable. Prediction of outcome has been difficult in individual patients based on laboratory data. In some patients with DCM, myocardial damage secondary to viral or immune-mediated myocardial inflammation may persist. To objectively assess inflammation, we measured plasma concentrations of C-reactive protein (CRP) in 188 patients with idiopathic DCM over 5-8 years. All had dyspnea and fatigue at rest; all patients had a left ventricular ejection fraction less than 40% by echocardiography or by contrast or radionuclide ventriculography. We divided these patients into two groups: patients dying within 5 years following admission (n = 49) and the remainder surviving for at least 5 years (n = 139). CRP concentrations in the patients dying early were significantly higher than in the long-term survivors (1. 05 +/- 1.37 vs. 0.49 +/- 1.04 mg/dl, p < 0.05). Sixty-two percent of the patients with CRP>1.0 died within 5 years. In addition to other laboratory tests including electrocardiography and echocardiography, routine CRP measurements proved to be valuable for identifying high-risk patients who require special treatment strategies.     

Different effects of cardiac resynchronization therapy on left atrial function in patients with either idiopathic or ischaemic dilated cardiomyopathy: a two-dimensional speckle strain study.

AIMS: In dilated cardiomyopathy (DCM), attenuation of left atrial (LA) booster pump function has been observed, and attributed both to altered LA loading conditions owing to left ventricular (LV) diastolic dysfunction and to LA involvement in the myopathic process. The aim of the present study was to detect LA systolic dysfunction in DCM using speckle-tracking two-dimensional strain echocardiography (2DSE), and to assess the effects of cardiac resynchronization therapy (CRT) on LA myocardial strain during 6 month follow-up. METHODS AND RESULTS: A total of 90 patients (aged, 52.4 +/- 10.2 years) with either idiopathic (n = 47) or ischaemic (n = 43) DCM underwent standard Doppler echo and 2DSE analysis of atrial longitudinal strain in the basal segments of LA septum and LA lateral wall, and in LA roof. The two groups were comparable for clinical variables (NYHA class: III in 72.2%; IV in 27.8%). LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler transmitral inflow measurements. LA diameter and maximal volume were also similar between the two groups. Conversely, LA active emptying volume and fraction were both lower in patients with idiopathic DCM. Peak systolic myocardial atrial strain was significantly compromised in patients with idiopathic DCM compared with ischaemic DCM in all the analysed atrial segments (P < 0.001). At follow-up, 64 patients (71.1%) (37 idiopathic and 27 ischaemic) were responders, and 26 (28.9%) (10 idiopathic; 16 ischaemic) were non-responders to CRT (responder: decrease of LV end-systolic volume >15%). A significant improvement in LA systolic function was obtained only in patients with ischaemic DCM responders to CRT (P < 0.001). By multivariable analysis, in the overall population, it was found that ischaemic aetiology of DCM (beta-coefficient = 0.62; P < 0.0001) and positive response to CRT (beta-coefficient = 0.42; P < 0.01) were the only independent determinants of LA lateral wall systolic strain. CONCLUSIONS: Two-dimensional strain represents a promising non-invasive technique to assess LA atrial myocardial function in patients with DCM. LA pump and reservoir function at baseline and after CRT are more depressed in idiopathic compared with ischaemic DCM patients. Future longitudinal studies are warranted to understand further the natural history of LA myocardial function, the extent of reversibility of LA dysfunction with CRT, and the possible prognostic impact of such indexes in patients with congestive heart failure.     

Duale Sequenzmethode zur Analyse der spontanen Baroreflexsensitivit?t bei Patienten mit dilatativer Kardiomyopathie

The analysis of heart rate variability (HRV) and blood pressure variability (BPV) improves the characterization of patients with dilated cardiomyopathy (DCM). In this study we tested the hypothesis that patients with DCM and controls show a different behavior in the baroreflex (BR) regulation. In contrast to other methods, the new dual sequence method (DSM) analyzes the baroreflex sensitivity (BRS) as a response of the heart rate (interbeat interval, IBI) on dual spontaneous fluctuations of blood pressure (BP). The DSM includes the analysis of bradycardiac fluctuations (an increase of BP causes an increase of IBI) and tachycardiac fluctuations (decrease of BP causes a decrease of IBI) to obtain enhanced information about the sympathetic-vagal regulation. DCM patients show a 40-50% lower number of correlated blood pressure-heart rate fluctuations (DCM patients: male 154 +/- 93, female 93 +/- 40 vs. control group: m 245 +/- 112, f 150 +/- 55, p < 0.05). The BRS in DCM patients is significantly lower than in controls (5.2 +/- 1.9 vs. 8.0 +/- 5.4 (ms/mm Hg), p < 0.05). Using the DSM the discriminant function analysis (6 parameters) classifies correctly 84% of DCM patients and the control group. Using the classical sequence method, only 76% were correctly classified. The DSM is a useful method for analyzing the BRS based on the spontaneous BR to obtain an increased classification of patients with DCM. BRS in patients with DCM is significantly reduced and apparently more ineffective.     

Myocardial ultrasonic tissue characterization for estimating histological abnormalities in hypertrophic cardiomyopathy: comparison with endomyocardial biopsy findings.

AIMS: In this study, we investigated the clinical usefulness of ultrasonic tissue characterization with integrated backscatter for the evaluation of myocardial histological abnormalities in comparison with endomyocardial biopsy findings in patients with hypertrophic cardiomyopathy. METHODS: Twenty patients with hypertrophic cardiomyopathy and 20 normal subjects were enrolled in this study. We measured two parameters for the ultrasonic tissue characterization with integrated backscatter: the magnitude of the cardiac-cycle-dependent variation in integrated backscatter signals (cdv-IB) and the mean value of integrated backscatter signals calibrated by the pericardium (cal-IB). These parameters were measured at both the interventricular septum and the left ventricular posterior wall. Histological findings of right ventricular endomyocardial biopsy specimens were analyzed by computer image analyzer. RESULTS: cdv-IB was significantly lower and cal-IB significantly higher in both the interventricular septum and the left ventricular posterior wall in patients with hypertrophic cardiomyopathy compared with normal subjects. In patients with hypertrophic cardiomyopathy, the degree of myocardial disarray, interstitial fibrosis, and nonhomogeneity of myocyte size showed positive correlations with cal-IB and negative correlations with cdv-IB. CONCLUSIONS: Ultrasonic tissue characterization with IB enables the noninvasive evaluation of myocardial histological abnormalities in patients with hypertrophic cardiomyopathy.     

Prognostic implication of myocardial texture analysis in idiopathic dilated cardiomyopathy.

BACKGROUND AND AIM: Abnormal myocardial acoustic properties have been reported in patients with idiopathic dilated cardiomyopathy (IDC). The aim of this study was to investigate the relationship between quantitative ultrasonic textural alterations of myocardium and clinical outcome in IDC. METHODS: Baseline clinical and echocardiographic variables were obtained from 28 patients with IDC. By using a videodensitometric approach, quantitative myocardial texture analysis was performed on images obtained from septum and posterior wall (PW). Cyclic variation (CV) index of mean gray level (MGL) was calculated according to the formula: (MGLdiast-MGLsyst)/MGLdiastx100. All patients were followed for an average of 11+/-5 months for the occurrence of cardiac death or repeated hospitalization due to worsening of heart failure. RESULTS: During follow-up, 10 patients experienced cardiac events (6 cardiac deaths and 4 heart failure events). The CV indexes of both septum and PW were significantly lower in patients with cardiac events than those of event free patients (6.8+/-9.6% vs. 13.6+/-8.2%, P<0.05 and 5.3+/-6.4% vs.15.7+/-7.2% P<0.001, respectively). Univariate analysis defined the following variables as predictors of outcome: PW-CV index (chi2=13.0, P=0.0003), transmitral E/A ratio (chi2=12.5, P=0.0004), symptom status (chi2=8.7, P=0.003), and septum-CV index (chi2=4.7, P=0.03). Multivariate stepwise regression analysis showed that the PW-CV index (chi2=7.5, P=0.006) and E/A ratio (chi2=6.5, P=0.01) were the independent predictors of outcome. The event-free survival rate of patients with PW-CV index <11% was significantly lower than those with an index > or = 11 (35.7% vs. 92.8%, P=0,001). CONCLUSION: The assessment of severely depressed CV index provides valuable prognostic information in patients with IDC.     

Assessment of the relationship between functional capacity and right ventricular ultrasound tissue characterization by integrated backscatter in patients with isolated mitral stenosis

AIM: The aim of the present study was to investigate right ventricular (RV) myocardial textural properties in asymptomatic and symptomatic mitral stenosis (MS) patients with normal RV systolic function using integrated backscatter (IBS). METHODS: The study included 40 patients with MS of moderate or severe degree. Patients were classified into 2 groups according to NYHA class (asymptomatic group, NYHA class I, symptomatic group, NYHA class II-III). RV pulsed-wave tissue Doppler imaging (TDI) and IBS analyses were performed in all patients. Isovolumic contraction time (IVCT), systolic wave velocity (S), isovolumic relaxation time (IVRT), early diastolic wave velocity (E), and late diastolic wave velocity (A) were measured by TDI. IBS amplitude (IB) and cyclic variation (CV) of the RV lateral wall in the parasternal long-axis view were measured by IBS. CV was calculated by subtracting systolic IB from diastolic IB. RESULTS: IVRT (54.2 +/- 11.9 ms versus 86.2 +/- 16.2 ms, P < 0.001) and A wave amplitude (10.2 +/- 2.1 cm/s versus 13.6 +/- 1.8 cm/s, P < 0.05) were higher whereas E wave amplitude (11.7 +/- 1.6 cm/s and 10.3 +/- 1.5 cm/s, P < 0.05) and E/A ratio (1.3 +/- 0.3 versus 0.7 +/- 0.1, P < 0.001) were lower in group 2. Symptomatic patients had a lower CV value of RV (9.5 +/- 3.4 dB versus 6.7 +/- 1.9 dB, P = 0.004). There was a positive correlation between CV and E/A (r = 0.964, P < 0.001) CONCLUSION: Symptomatic isolated MS patients had RV echo texture changes and diastolic dysfunction in comparison to asymptomatic ones with similar mitral valve areas in the presence of normal RV systolic function. In isolated MS, both pulsed-wave TDI and IBS may aid in the detection of RV diastolic pathology.     

Assessment of arterial medial characteristics in human carotid arteries using integrated backscatter ultrasound and its histological implications

Recently, ultrasound tissue characterization of the carotid arteries with an integrated backscatter (IB) analysis was shown to identify a high-risk group of atherosclerosis. To clarify whether IB ultrasound is useful in assessing arterial sclerosis as well as stiffness beta and whether IB values reflect the histological structure, we measured IB values of common carotid media in 52 subjects without coronary risk factors and in 10 patients with systemic sclerosis (SSc) in the clinical studies and 12 patients in the histological studies with a Philips Medical Systems Sonos 5500. IB values were correlated with age (r=0.69, P<0.0001), intima-media thickness (r=0.72, P<0.0001) and stiffness beta (r=0.80, P<0.0001) in the control subjects. IB values and stiffness beta in the SSc group were greater than in an age- and sex-matched control group (IB values: 9.6+/-2.7dB versus 16.1+/-1.8dB; stiffness beta: 11.5+/-4.5 versus 20.6+/-5.6, P<0.01). IB values of the media were correlated with the elastic fragmentation index (r=0.63, P=0.029) and the collagen fiber index (r=0.59, P=0.046). Measurements of IB values of carotid media are useful for non-invasively evaluating arterial sclerosis.     

Function of the right ventricle in patients with dilated cardiomyopathy]

To analyze right-ventricular size and function and their relationship to left-ventricular dimensions in patients with dilated cardiomyopathy (DCM), biplane cineventriculography was performed in 57 patients. The results were compared to 15 normals (N). In patients dilatation of the right ventricle (RVEDVI: DCM: 126.5 +/- 41.4 ml/m2, N: 90.5 +/- 9.2 ml/m2, 2 p < 0.05) was less pronounced than dilatation of the left ventricle (LVEDVI: DCM: 136.0 +/- 45.8 ml/m2, N: 76.7 +/- 7.9 ml/m2, 2 p < 0.05). Left-ventricular ejection fraction (LVEF: DCM: 36.1 +/- 10.2%, N: 64.4 +/- 3.8%, 2 p < 0.05) was more reduced than right-ventricular ejection fraction (RVEF: DCM: 39.7 +/- 11.5%, N: 58.3 +/- 3.3%, 2 p < 0.05). Concerning the individual patient, a good correlation was found between right- and left-ventricular stroke volume (r = 0.74), whereas ejection fraction (r = 0.58), enddiastolic (r = 0.52) and endsystolic volume (r = 0.55) of the left and right ventricle correlated only moderately. Twenty-three of the 57 patients showed pronounced differences between right- and left-ventricular ejection fraction. The difference RVEF-LVEF was < = -10% in six patients, i.e., right-ventricular ejection fraction was markedly more reduced than left-ventricular ejection fraction. Right-ventricular myocardial biopsy was performed in five of these six patients with histologic evidence of dilated cardiomyopathy and, also, no signs of right-ventricular dysplasia (no lipomatous tissue replacement).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mitral effective regurgitant orifice area versus left ventricular ejection fraction as prognostic indicators in patients with dilated cardiomyopathy and heart failure.

BACKGROUND: This study aimed at investigating the relative powers of the quantitative evaluation of functional mitral regurgitation (FMR) and ejection fraction (EF) in predicting the clinical changes and prognosis of dilated cardiomyopathy (DCM) with severe systolic dysfunction. METHODS: A total of 81 patients with DCM, EF < 0.40 and at least mild FMR were prospectively evaluated during a mean follow-up of 24 +/- 7 months. Twenty cardiac deaths were recorded. At the time of enrolment all patients underwent echocardiographic evaluation of the effective regurgitant orifice area (ERO), EF, left atrial area, and tenting area. In 42/81 patients, the data obtained at enrolment were compared to those measured at a mean follow-up of 10 +/- 2 months. A multivariate analysis was performed to determine the best predictor of NYHA class and mortality. RESULTS: There was a correlation between the NYHA class and the ERO (chi2 = 26.1, p = 0.0001) but not with EF (chi2 = 4.3, p = 0.22) and at multivariate analysis, the ERO was found to be the main determinant of the NYHA class (r = 0.64, standard error 0.6, p = 0.0001). The NYHA class remained unchanged or improved in 28/42 (67%) and deteriorated in 14/42 (33%) patients. In the first group, the ERO increased from 22.3 +/- 10 to 30.2 +/- 16.4 mm2 (p = 0.05) and the tenting area from 5.8 +/- 1.8 to 6.8 +/- 1.8 cm2 (p = 0.001); in the second group, the ERO increased from 25.1 +/- 5.6 to 39.0 +/- 14.5 mm2 (p = 0.04) and the tenting area from 5.9 +/- 2.1 to 7.6 +/- 1.8 cm2 (p = 0.0001), in both groups without significant changes in EF. The mortality was 8.1% in patients with an ERO < 21 mm2, 30.3% in patients with an ERO of 21-30 mm2, and 50% in those with an ERO > 30 mm2. The EF was similar in the three subgroups. At Cox multivariate analysis the best predictors of mortality were the ERO (chi2 = 13.83, p = 0.0001), EF (chi2 = 5.48, p = 0.019), and left atrial area (chi2 = 4.52, p = 0.04). CONCLUSIONS: FMR in DCM well correlated with the clinical status of the patients and its worsening was suggestive of progression of the disease. The ERO was found to be the best predictor of the NYHA class and mortality.     

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.