Yasuji Doi

Development of different phenotypes of hypertensive heart failure: systolic versus diastolic failure in Dahl salt-sensitive rats.

Objective There are two phenotypes of heart failure, systolic failure and isolated diastolic heart failure with preserved left ventricular systolic function. Although isolated diastolic heart failure frequently occurs, there are only models for diastolic dysfunction unassociated with heart failure and models with overt diastolic heart failure have not been established. We attempted to develop two different models, i.e. diastolic and systolic failure models, based on hypertension. Materials and methods Dahl salt-sensitive rats were placed on 8% NaCl diet from 7 weeks old (7-week starting group) or 8 weeks old (8-week starting group). As an age-matched control, Dahl salt-sensitive rats were consistently placed on normal chow. In these rats, echocardiogram was serially recorded, followed by hemodynamic and histological studies. Results The 7-week starting rats showed a steep elevation in blood pressure and progressive left ventricular hypertrophy, and fell into overt heart failure at approximately 19 weeks. The development of heart failure was not associated with a decrease in left ventricular midwall fractional shortening or an increase in left ventricular end-diastolic dimension as compared with the age-matched control, which mimics the characteristics of clinically observed isolated diastolic heart failure. The 8-week starting rats showed a gradual rise in blood pressure and less progressive left ventricular hypertrophy, and fell into heart failure at approximately 26 weeks with a decrease in mid-wall fractional shortening and an increase in left ventricular end-diastolic dimension. Hemodynamic and histological studies at failing stage revealed comparable elevation of left ventricular end-diastolic pressure and comparable left ventricular fibrosis in both groups. Conclusion These two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolic heart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.

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.

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.

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.

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.

Abnormal coronary flow dynamics at rest and during tachycardia associated with impaired left ventricular relaxation in humans : implication for tachycardia-induced myocardial ischemia

OBJECTIVES This study attempted to clarify the effect of ventricular relaxation abnormalities on coronary flow dynamics at rest and during tachycardia in humans. BACKGROUND Ventricular relaxation abnormality has been demonstrated in animals to have an adverse impact on early diastolic coronary flow dynamics. However, this relation has not been established in humans. Even if the adverse effect were latent at rest, it might become evident during tachycardia because tachycardia reduces coronary flow reserve and facilitates the production of myocardial ischemia. METHODS Doppler phasic left coronary flow velocity pattern was obtained at rest and during tachycardia in 23 patients without coronary stenosis. The time constant of left ventricular isovolumic pressure (tau) was used to assess ventricular relaxation. RESULTS The time to peak flow velocity of the diastolic coronary flow wave was longer, and the fraction of the first third of diastolic coronary flow was smaller, in patients with a longer tau (r = 0.58, p < 0.01; r = -0.44, p < 0.05), indicating a close relation between early diastolic coronary flow dynamics and ventricular relaxation. Although rapid atrial pacing yielded an increase in the coronary flow velocity integral per minute in all patients, diastolic coronary flow velocity integral per minute increased in 9 patients with a normal (< or = 40 ms) tau at rest but decreased in 14 patients with a longer (> 40 ms) tau at rest. CONCLUSIONS Impaired left ventricular relaxation was associated with decreased coronary flow in early diastole at rest and decreased coronary flow throughout diastole during tachycardia in patients without coronary stenosis. These findings may provide more insight into the mechanism of tachycardia-induced subendocardial ischemia in patients with impaired ventricular relaxation but without concomitant coronary stenosis.

Myocardial integrated ultrasonic backscatter in patients with old myocardial infarction: Comparison with radionuclide evaluation

The purpose of our study was to clarify whether the abnormalities in integrated backscatter may be used to assess myocardial viability in patients with old myocardial infarction by comparing these integrated backscatter parameters with conventional radionuclide and echocardiographic estimates of myocardial viability. Two myocardial integrated backscatter parameters, the magnitude of cyclic variation in integrated backscatter and the myocardial integrated backscatter calibrated with the power of Doppler signals from the blood along the same ultrasound beam (calibrated myocardial integrated backscatter), were measured in 21 normal persons and 33 patients with old anteroseptal myocardial infarction. Calibrated myocardial integrated backscatter was higher and the magnitude of cyclic variation in integrated backscatter was lower in the infarct septum compared with the septum of normal subjects. Percent thallium uptake, as assessed in scintigraphic images taken at rest or after reinjection, correlated well with the calibrated myocardial integrated backscatter (r = -0.72, p < 0.01) and more weakly but significantly with the magnitude of cyclic variation in integrated backscatter (r = 0.55, p < 0.05) in 16 of 33 patients. The measurement of calibrated myocardial integrated backscatter, in addition to the magnitude of cyclic variation of integrated backscatter, may likely be valuable in the noninvasive assessment of myocardial viability.

Dobutamine stress ultrasonic myocardial tissue characterization in patients with dilated cardiomyopathy.

Although acoustic properties of the myocardium are different between patients with cardiomyopathy and normal subjects, the frequency of the abnormal properties in patients with cardiomyopathy is unknown. We assessed the frequency of abnormal acoustic properties of the myocardium detectable with integrated backscatter in patients with cardiomyopathy and attempted more sensitive ultrasonic tissue characterization by combining dobutamine stress testing in patients with cardiomyopathy with apparently normal acoustic properties of the myocardium at rest. The magnitude of cyclic variation of integrated backscatter and calibrated myocardial integrated backscatter at end diastole were measured in 36 normal subjects and 40 patients with dilated cardiomyopathy. Either one of the integrated backscatter parameters was abnormal in 30 of 40 patients with cardiomyopathy. Dobutamine stress ultrasonic tissue characterization was performed in 10 patients with cardiomyopathy with normal values of both integrated backscatter parameters and 10 normal subjects. Calibrated myocardial integrated backscatter did not change during dobutamine infusion in any subject. The magnitude of cyclic variation in integrated backscatter increased in normal subjects but did not change in patients with cardiomyopathy despite a comparative associated increase in the systolic wall thickening during dobutamine infusion. Abnormal acoustic properties are detectable at rest with myocardial integrated backscatter about in three quarters of patients with cardiomyopathy. A combination of dobutamine stress testing would provide more sensitive ultrasonic myocardial tissue characterization and may make it possible to detect subtle changes in the acoustic properties of the myocardium in patients with dilated cardiomyopathy. Therefore dobutamine stress ultrasonic tissue characterization may detect mild dilated cardiomyopathy.

Peak Early Diastolic Filling Velocity May Decrease With Preload Augmentation: Effect of Concomitant Increase in the Rate of Left Atrial Pressure Drop in Early Diastole

Doppler-determined transmitral flow velocity pattern has been shown to depend on transmitral pressure gradient, and left atrial (LA) pressure has been considered to be important in determining transmitral pressure gradient in early diastole and peak early diastolic filling velocity (E). In recent studies in human beings, however, it was proved that E did not necessarily change with LA pressure. This may be because concomitant changes in other factors masked the effect of LA pressure. To investigate the relation between transmitral flow velocity pattern and hemodynamic parameters during preload intervention over the wide range of LA pressure, pulsed Doppler transmitral flow velocity pattern and high-fidelity LA and left ventricular (LV) pressures were simultaneously recorded during rapid volume loading to the LA. Data at three stages, at control, at moderate volume loading (the median LA-to-LV crossover pressure during the volume loading), and at advanced volume loading (the maximal crossover pressure during the volume loading), were compared with one another in 11 dogs. A mean value of E increased with the crossover pressure up to moderate volume loading but did not further increase at advanced volume loading. In the data pooled from all experimental stages in all dogs, the changes in E did not correlate with those in the crossover pressure, but correlated weakly with those in the difference between the crossover pressure and LV minimum pressure (r = 0.45, p < 0.05). E decreased at advanced volume loading in three of 11 dogs with a steep LA pressure drop in early diastole although the changes in the difference between the crossover pressure and LV minimum pressure in the three dogs were similar to those in the other eight dogs. The changes in a rate of LA pressure drop in early diastole associated with advanced volume loading inversely correlated with those in E (r = -0.79, p < 0.01). Thus, E may decrease with an extreme increase in LA pressure; this change may be due to an associated increase in a rate of LA pressure drop in early diastole. This finding suggests that at high LA pressure the increased rate of LA pressure drop in early diastole appears to decrease LV filling and hence to reduce stroke volume.