Johji Naito

Endothelial dysfunction in the early stage of atherosclerosis precedes appearance of intimal lesions assessable with intravascular ultrasound

The objective of this study was to clarify whether morphologic evaluation of the in vivo artery with intravascular ultrasound provides as sensitive a marker as endothelial dysfunction or microscopic histologic assessment. Endothelial dysfunction assessed with the changes in the vessel diameter during acetylcholine infusion has been used as a more sensitive marker of atherosclerosis than the angiographic estimates of morphologic structure of the vessel. Recent advent of intravascular ultrasound has provided such high-resolution images of the vessels that morphologic changes in the vessel structure are sensitively and accurately detected. Twenty-two rabbits were divided into three groups: six rabbits fed a cholesterol-rich diet for 2 weeks as the hypercholesterolemia group, eight rabbits fed with the diet for 8 weeks as the atherosclerosis group, and eight rabbits fed a normal diet as the normal group. After evaluating the atherosclerotic lesions by intravascular ultrasound, the cross-sectional area was measured in the baseline and during the infusion of acetylcholine (0.05, 0.5, and 5 micrograms/kg/min) and nitroglycerin (5 micrograms/kg/min). No atherosclerotic lesions were detectable with intravascular ultrasound in any rabbit despite the presence of microscopic intimal lesions in the vessels in the rabbits of the atherosclerosis group. The cross-sectional area increased during acetylcholine infusion in the rabbits of the normal and the hypercholesterolemia groups. In contrast, in the rabbits of the atherosclerosis group, the cross-sectional area did not significantly increase during acetylcholine infusion at the rate of 0.5 microgram/kg/min and even tended to decrease at the rate of 5 micrograms/kg/min (-3.8% +/- 3.7%, P < 0.05 vs the normal group). Dilating responses to nitroglycerin infusion were similar among all three groups. In conclusion, impairment of the endothelium-dependent vasodilating response assessed with intravascular ultrasound in the in vivo vessel precedes the appearance of echographic atherosclerotic findings. Thus intravascular ultrasound, if used in combination with drug intervention to assess endothelial function, would provide even more accurate assessment of the vessels than conventional intravascular ultrasound alone.

Analysis of transmural trend of myocardial integrated ultrasound backscatter for differentiation of hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension

OBJECTIVES This study was undertaken to differentiate hypertrophic cardiomyopathy from hypertensive hypertrophy using a newly developed M-mode format integrated backscatter imaging system capable of calibrating myocardial integrated backscatter with the power of Doppler signals from the blood. BACKGROUND Myocardial integrated ultrasound backscatter changes in patients with hypertrophic cardiomyopathy; however, it is unknown whether ultrasound myocardial tissue characterization may be useful in differentiating hypertrophic cardiomyopathy from hypertensive hypertrophy. METHODS Calibrated myocardial integrated backscatter and its transmural gradient were measured in the septum and posterior wall in 31 normal subjects, 13 patients with hypertensive hypertrophy and 22 patients with hypertrophic cardiomyopathy. The gradient in integrated backscatter was determined as the ratio of calibrated integrated backscatter in the endocardial half to that in the epicardial half of the myocardium. RESULTS Cyclic variation of integrated backscatter was smaller and calibrated myocardial integrated backscatter higher in patients with hypertrophied hearts than in normal subjects, but there were no significant differences in either integrated backscatter measure between patients with hypertensive hypertrophy and those with hypertrophic cardiomyopathy. Transmural gradient in myocardial integrated backscatter was present only in patients with hypertrophic cardiomyopathy (5.0 +/- 1.8 dB [mean +/- SD] for the septum; 1.2 +/- 1.6 dB for the posterior wall). CONCLUSIONS Hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension can be differentiated on the basis of quantitative analysis of the transmural gradient in integrated backscatter.

Ultrasonic myocardial tissue characterization in patients with dilated cardiomyopathy: Value in noninvasive assessment of myocardial fibrosis

Dilated cardiomyopathy (DCM) is usually diagnosed from the left ventricular functional viewpoint by the detection of dilated ventricular cavity and depressed myocardial contractility. Although histologic analysis of the myocardium no doubt provides clinically important information, it is possible only with microscopic examination of biopsy specimen of the myocardium. The objective of this particular study is to clarify the comparative values of the measures of ultrasonic tissue characterization, that is, calibrated myocardial integrated backscatter (IB) and the magnitude of cyclic variation in IB, with conventional echocardiographic parameters in assessing histologic condition of the myocardium. The magnitude of cyclic variation in IB and myocardial IB at end-diastole calibrate with the power of Doppler signals from the blood were measured in addition to conventional echocardiographic parameters in 14 patients with DCM. Calibrated myocardial IB was higher in patients with more fibrosis in the biopsy specimen of the heart tissue, whereas the magnitude of variation in IB or conventional echocardiographic parameters did not significantly correlate with a histologic estimate of myocardial fibrosis. Calibrated myocardial IB provides information about the myocardial fibrosis that cannot be assessable with conventional echocardiographic parameters. Calibrated myocardial IB and the magnitude of cyclic variation of IB are likely to reflect somewhat different acoustic properties of the myocardium.

Digital Subtraction High-Frame-Rate Echocardiography in Detecting Delayed Onset of Regional Left Ventricular Relaxation in Ischemic Heart Disease

BACKGROUND Because left ventricular (LV) diastolic function is impaired before systolic function in patients with ischemic heart disease and because ischemic heart disease is constituted of regional rather than global abnormalities of the left ventricle, measures of LV regional diastolic dysfunction, if possible, should provide the most sensitive assessment of the coronary involved region. The objectives of this study are to clarify whether high-frame-rate two-dimensional echocardiography, combined with digital subtraction image processing, may be used to visualize regional LV relaxation abnormalities in patients with ischemic heart disease and to clarify whether this technique provides a measure for the noninvasive assessment of the coronary involved region. METHOD AND RESULTS In 30 normal subjects and 59 patients with ischemic heart disease, two-dimensional echocardiograms obtained at a rate of 60 frames per second were provided on line for digital subtraction analysis, with which digitized images were continuously subtracted on a frame-by-frame basis. The subtracted images were analyzed to determine the onset of the segmental outward motion of the LV wall in early diastole in each of 16 segments per subject. Regional relaxation index, defined as the interval from the second heart sound to the onset of outward wall motion, was significantly prolonged in the coronary involved segments compared with the normal segments (36.3 +/- 18.0 versus 101.2 +/- 34.0 ms, P < .01). The prolongation in the regional relaxation index was observed even in the coronary involved segments without reduction in systolic wall motion. When a cutoff level of 50.0 ms was used, coronary involved segments could be distinguished from normal or border segments with a sensitivity of 92% and a specificity of 81%. CONCLUSIONS Digital subtraction high-frame-rate echocardiography may be used to visualize regional LV relaxation abnormalities in patients with ischemic heart disease. The time interval from the second heart sound to the onset of the segmental outward motion of the LV wall (regional relaxation index) obtained with this technique provides a noninvasive and accurate measure for assessing coronary involved regions.

Importance of left ventricular minimal pressure as a determinant of transmitral flow velocity pattern in the presence of left ventricular systolic dysfunction

OBJECTIVES This study was designed to assess whether the transmitral flow velocity pattern provides an estimation of left atrial pressure irrespective of the presence of left ventricular systolic dysfunction and, if not, to clarify the mechanism. BACKGROUND The pulsed Doppler transmitral flow velocity pattern, particularly peak early diastolic filling velocity, has been shown to change in parallel with left atrial pressure. However, extremely elevated left atrial pressure in association with heart failure does not necessarily cause an increase in peak early diastolic filling velocity in patients. METHODS Left atrial pressure was elevated with intravenous saline infusion in 11 dogs (normal left ventricular function group) and hemodynamic, transesophageal Doppler echocardiographic and M-mode echocardiographic variables were recorded at three different loading levels. In another 12 dogs, left atrial pressure was elevated by production of left ventricular systolic dysfunction with the stepwise injection of microspheres into the left coronary artery (left ventricular dysfunction group) and the same set of recordings was obtained at three different levels of dysfunction. RESULTS Peak early diastolic filling velocity increased with left atrial pressure in the normal left ventricular function group and correlated with mean left atrial pressure (r = 0.61, p < 0.01) and early diastolic left atrial to left ventricular crossover pressure (r = 0.71, p < 0.01). In contrast, peak early diastolic filling velocity did not increase with left atrial pressure in the left ventricular dysfunction group and did not correlate with mean left atrial pressure (r = -0.05) or the crossover pressure (r = 0.06). Peak early diastolic filling velocity correlated well with the difference between the crossover pressure and left ventricular minimal pressure in the left ventricular dysfunction group (r = 0.64, p < 0.01). In contrast to peak early diastolic filling velocity, deceleration time of the early diastolic filling wave correlated with mean left atrial pressure and the crossover pressure irrespective of the primary cause of preload alteration (r = -0.54, r = -0.59, p < 0.01 respectively, n = 69 for all data). CONCLUSIONS Preload dependency of the Doppler transmitral flow velocity pattern is hampered if an increase in left atrial pressure is due to left ventricular systolic dysfunction. In this setting, the increase in left ventricular minimal pressure due to left ventricular systolic dysfunction cancels the effect of the increase in left atrial pressure on the flow velocity pattern.

Doppler echocardiographic pulmonary venous flow-velocity pattern for assessment of the hemodynamic profile in acute congestive heart failure

The hemodynamic profile of congestive heart failure (CHF) is best described in terms of its two primary sets of hemodynamic parameters, that is, left atrial pressure and cardiac output, each of which has a specific and independently variable hemodynamic cause. To assess whether analysis of the mitral and/or pulmonary venous flow-velocity patterns provides valuable information in the noninvasive assessment of the hemodynamic profile of CHF, these patterns were obtained by using the transthoracic approach in 18 patients with acute CHF with simultaneous measurements of catheter-derived mean pulmonary capillary wedge pressure and thermodilution cardiac index. Measurements were repeated on two occasions in each case: at the acute stage of CHF and 1 to 5 days after treatment. Peak diastolic pulmonary venous forward flow velocity was higher, the ratio of pulmonary venous systolic to diastolic peak forward flow velocity was lower, and the ratio of mitral early diastolic to late diastolic flow velocity was greater in patients with higher mean pulmonary capillary wedge pressure (r = 0.80, n = 36, p < 0.01; r = -0.69, n = 36, p < 0.01; r = 0.71, n = 36, p < 0.01). Peak systolic pulmonary venous forward flow velocity and time-velocity integral of the systolic pulmonary venous flow wave were greater in patients with larger cardiac index (r = 0.80, n = 36, p < 0.01; r = 0.62, n = 36, p < 0.01). In conclusion, two primary sets of hemodynamic parameters, that is, left atrial pressure and cardiac output, can be estimated with Doppler pulmonary venous flow parameters in patients with acute CHF.

Noninvasive Assessment of Left Ventricular Relaxation Using Continuous-Wave Doppler Aortic Regurgitant Velocity Curve Its Comparative Value to the Mitral Regurgitation Method

BACKGROUND The most established parameters of left ventricular (LV) relaxation are peak negative value of the first derivative of LV pressure (-dP/dtmax) and the time constant of isovolumic LV pressure fall. The instantaneous pressure gradient between the aorta and the LV during diastole can be calculated from the continuous-wave Doppler aortic regurgitant velocity spectrum. Because the fluctuation of aortic pressure during LV isovolumic relaxation is negligibly minor and because LV minimal pressure is negligibly low, LV pressure during the isovolumic relaxation period may be derived from the continuous-wave Doppler aortic regurgitant velocity spectrum. This study was designed to clarify whether analysis of continuous-wave Doppler aortic regurgitation recording provides accurate measures of LV relaxation over a wide range of LV function and to determine comparative values of aortic and mitral regurgitation methods in the assessment of LV relaxation. METHODS AND RESULTS In eight mongrel dogs with acute ischemic LV dysfunction, the continuous-wave Doppler aortic regurgitant velocity spectrum was recorded simultaneously with high-fidelity LV and aortic pressures, while the continuous-wave Doppler mitral regurgitant velocity spectrum was recorded simultaneously with high-fidelity left atrial and LV pressures. The aortic regurgitant velocity spectrum was provided for the determination of Doppler-derived mean rate of LV pressure fall in 20 ms after the onset of aortic regurgitation (delta P/delta t-AR) and the time interval from the onset of aortic regurgitation to the point at (1-1/e)1/2 of the maximal aortic regurgitant velocity as an estimate of the time constant. The mitral regurgitant velocity spectrum was provided for Doppler-derived mean rate of LV pressure fall in 20 ms after the point of -dP/dtmax (delta P/delta t-MR) and the time interval from the point of -dP/dtmax to the point with mitral regurgitant velocity of (1/e)1/2 of the mitral regurgitant velocity at the point of -dP/dtmax as an estimate of the time constant. delta P/delta t-AR and delta P/delta t-MR correlated well with catheter-derived -dP/dtmax (r = .92, r = .98, P < .01, respectively). The time constant derived from aortic and mitral regurgitant velocity spectra (tau-AR and tau-MR) also correlated well with catheter-derived time constant (r = .84, r = .76, P < .01, respectively). However, a mean difference of the catheter-derived time constant minus tau-MR was larger than tau-AR (29 +/- 30 versus 4 +/- 17 ms, P < .01, presented as mean +/- 2 SD). CONCLUSIONS LV relaxation can be assessed from the continuous-wave Doppler aortic regurgitant velocity spectrum. The aortic regurgitation method provides an even more accurate estimate of the time constant compared with the mitral regurgitation method, particularly in the presence of LV dysfunction.

Validation of transthoracic myocardial ultrasonic tissue characterization: comparison of transthoracic and open-chest measurements of integrated backscatter

To investigate whether myocardial integrated backscatter (IB) can be measured through the chest wall, myocardial IB parameters were measured in five adult mongrel dogs with a newly developed IB imaging system capable of measurements of myocardial IB relative to backscatter from the blood. There was no significant difference in the calibrated myocardial IB between the closed chest and the open chest conditions either in the septum or in the posterior wall if a 2.5- or 3.5-MHz frequency transducer was used. There was no significant difference in the magnitude of cyclic variation in IB between the closed chest and the open chest conditions independent of the frequency of the transducer used. These data suggest that we can accurately measure not only the magnitude of cyclic variation in IB but also the calibrated myocardial IB through the chest wall with a 2.5- or 3.5-MHz frequency transducer. Such data may validate measurements of myocardial IB parameters through the chest wall even in humans.

Transthoracic Doppler assessment of pattern of left ventricular dysfunction in hypertensive heart disease : Combined analysis of mitral and pulmonary venous flow velocity patterns

Although mitral flow velocity pattern changes with the progression of left ventricular (LV) diastolic dysfunction, it lacks predictive value in individual patients because of pseudonormalization in the presence of congestive heart failure and many physiologic and pathologic contributors to the mitral flow velocity pattern. To determine whether analysis of pulmonary venous flow velocity patterns complements the information obtainable from the mitral flow velocity patterns in the evaluation of patterns of LV dysfunction of hypertensive heart disease in individual patients, the ratio of the peak early diastolic filling velocity/peak filling velocity at atrial contraction (E/A ratio) in the mitral flow velocity pattern and the ratio of the peak systolic forward flow velocity (S)/peak diastolic forward flow velocity (D) (S/D ratio) in the pulmonary venous flow velocity pattern by the transthoracic approach were determined in 107 hypertensive patients with and without congestive heart failure. Age-related normal values of the E/A and S/D ratios were determined in 61 normal subjects and used to judge the normality or abnormality of the patterns. Results of the study indicate that (1) although an increased mitral E/A ratio is strongly indicative of heart failure with normal LV systolic function, the mitral E/A ratio is frequently within the normal range in hypertensive patients with heart failure; (2) association of decreased pulmonary venous S/D ratios with a normal mitral flow velocity pattern indicates the presence of heart failure as a result of LV systolic dysfunction that is usually observed at the most advanced pattern of LV dysfunction; (3) mild LV diastolic dysfunction is likely to exist in patients with normal E/A ratios if the pulmonary venous S/D ratio is higher than normal value; (4) predictive accuracy in the detection of LV systolic and diastolic dysfunction would be improved if both mitral and pulmonary venous flow velocity patterns rather than the mitral flow velocity pattern alone were analyzed. In conclusion, analysis of pulmonary venous flow velocity recordings improves accuracy and reliability of the Doppler assessment of LV systolic and diastolic dysfunction, particularly in individual hypertensive patients with normal mitral flow velocity patterns.

INFLUENCE OF PRELOAD, AFTERLOAD, AND CONTRACTILITY ON MYOCARDIAL ULTRASONIC TISSUE CHARACTERIZATION WITH INTEGRATED BACKSCATTER

Influence of hemodynamic changes in preload, afterload and contractility on myocardial integrated backscatter (IB) was studied in 26 adult mongrel dogs by measuring myocardial IB calibrated with the backscatter from the blood during volume infusion (preload alteration), during aortic constriction (afterload alteration), and during dobutamine or propranolol infusion (contractility alteration). Changes in preload, afterload or contractility did not significantly affect the calibrated myocardial IB either in the septum or in the posterior wall. Changes in preload and afterload did not affect the magnitude of cyclic variation in IB. However, dobutamine produced a significant increase in the magnitude of cyclic variation in IB and propranolol significantly decreased the magnitude of cyclic variation in IB. These data indicated that the calibrated myocardial IB is independent of preload, afterload and contractility, and that the magnitude of cyclic variation in IB is influenced by contractility. We may estimate static (related to histological changes such as fibrosis, edema, necrosis, and so on) and dynamic (related to myocardial contraction such as sarcomere length, muscle fiber orientation, and so on) properties of the myocardium more precisely using myocardial IB calibrated with the backscatter from the blood in addition to the magnitude of cyclic variation in IB.