OBJECTIVES:The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy.BACKGROUND:The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling.METHODS:At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.4 months. Serial echocardiographic measurements of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility calculated to 90% power at 5% significance defined detectable differences of 0.09 cm for LVIDd and 0.86% for EF.RESULTS:Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 +/- 0.5 versus 3.7 +/- 0.5 (cm/m(2)) and 26.6 +/- 7.3 versus 26.9 +/- 7.0 (%). Mean group changes from baseline over time were compared. Significant decrease in LVIDd and increase in EF began by four months, reached plateau by one year, and persisted to two years in valsartan compared with placebo patients, irrespective of age, gender, race, etiology, NYHA classification, and co-treatment therapy. Changes at 18 months were -0.12 +/- 0.4 versus -0.05 +/- 0.4 (cm/m(2)), p < 0.00001 for LVIDd, and +4.5 +/- 8.9 versus +3.2 +/- 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in EF were no different between valsartan and placebo groups.CONCLUSIONS:The Val-HeFT echocardiographic substudy of 5,010 patients with moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed LV remodeling.

The objective of this study was to use high-fidelity animal data and numerical simulations to gain more insight into the reliability of the estimated relaxation constant derived from left ventricular pressure decays, assuming a monoexponential model with either a fixed zero or free moving pressure asymptote. Comparison of the experimental data with the results of the simulations demonstrated a trade off between the fixed zero and the free moving asymptote approach. The latter method more closely fits the pressure curves and has the advantage of producing an extra coefficient with potential diagnostic information. On the other hand, this method suffers from larger standard errors on the estimated coefficients. The method with fixed zero asymptote produces values of the time constant of isovolumetric relaxation (tau) within a narrow confidence interval. However, if the pressure curve is actually decaying to a nonzero pressure asymptote, this method results in an inferior fit of the pressure curve and a biased estimation of tau.

The pressure-velocity relationship across the normal mitral valve is approximated by the Bernoulli equation DeltaP = 1/2 rhoDeltav(2) + M. dv/dt, where DeltaP is the atrioventricular pressure difference, rho is blood density, v is transmitral flow velocity, and M is mitral inertance. Although M is indispensable in assessing transvalvular pressure differences from transmitral flow, this term is poorly understood. We measured intraoperative high-fidelity left atrial and ventricular pressures and simultaneous transmitral flow velocities by using transesophageal echocardiography in 100 beats (8 patients). We computed mean mitral inertance (M) by M = integral((DeltaP)-(1/2 x rho v(2))dt/integral(dv/dt)dt and we assessed the effect of the inertial term on the transmitral pressure-flow relation. ranged from 1.03 to 5.96 g/cm(2) (mean = 3.82 +/- 1.22 g/cm(2)). DeltaP calculated from the simplified Bernoulli equation (DeltaP = 1/2. rhov(2)) lagged behind (44 +/- 11 ms) and underestimated the actual peak pressures (2.3 +/- 1.1 mmHg). correlated with left ventricular systolic pressure (r = -0.68, P < 0.0001) and transmitral pressure gradients (r = 0.65, P < 0.0001). Because mitral inertance causes the velocity to lag significantly behind the actual pressure gradient, it needs to be considered when assessing diastolic filling and the pressure difference across normal mitral valves.

The authors hypothesised that a measured mitral valve diameter and a color Doppler M-mode image of left ventricular inflow provide sufficient information for the non-invasive estimation of the left ventricular longitudinal impedance of left ventricular filling. The aim of this study was therefore (1) to develop the algorithms for calculation of left ventricular longitudinal impedance from a color Doppler M-mode image and (2) to study the feasibility of this calculation in an in vitro experiment. In a cardiovascular simulator consisting of a left ventricular pulse duplicator system connected to a hydraulic model of the arterial tree, color M-mode images of left ventricular inflow were captured. Pressure differences are calculated by implementing the Euler equation. Velocity at the level of the mitral valve is used for the calculation of flow. Pressure gradients and flow are used for calculation of the longitudinal impedance in the frequency domain. No influence on the amplitude of the calculated longitudinal impedance was observed (p>0.05) for a change in heart rate and systolic pressure. However, the calculated longitudinal impedance was significantly altered for a smaller valve and a different test fluid (p<0.05). In conclusion: longitudinal impedance of left ventricular inflow can be derived non-invasively from color Doppler M-mode images and provides a quantitative interpretation of the numerical velocity information in a color Doppler M-mode image with potential clinical useful information

Although alteration in pulmonary venous flow has been reported to relate to mitral regurgitant severity, it is also known to vary with left ventricular (LV) systolic and diastolic dysfunction. There are few data relating pulmonary venous flow to quantitative indexes of mitral regurgitation (MR). The object of this study was to assess quantitatively the accuracy of pulmonary venous flow for predicting MR severity by using transesophageal echocardiographic measurement in patients with variable LV dysfunction. This study consisted of 73 patients undergoing heart surgery with mild to severe MR. Regurgitant orifice area (ROA), regurgitant stroke volume (RSV), and regurgitant fraction (RF) were obtained by quantitative transesophageal echocardiography and proximal isovelocity surface area. Both left and right upper pulmonary venous flow velocities were recorded and their patterns classified by the ratio of systolic to diastolic velocity: normal (≥1), blunted (<1), and systolic reversal (<0). Twenty-three percent of patients had discordant patterns between the left and right veins. When the most abnormal patterns either in the left or right vein were used for analysis, the ratio of peak systolic to diastolic flow velocity was negatively correlated with ROA (r = –0.74, P < .001), RSV (r = –0.70, P < .001), and RF (r = –0.66, P < .001) calculated by the Doppler thermodilution method; values were r = –0.70, r = –0.67, and r = –0.57, respectively (all P < .001), for indexes calculated by the proximal isovelocity surface area method. The sensitivity, specificity, and predictive values of the reversed pulmonary venous flow pattern for detecting a large ROA (>0.3 cm2) were 69%, 98%, and 97%, respectively. The sensitivity, specificity, and predictive values of the normal pulmonary venous flow pattern for detecting a small ROA (<0.3 cm2) were 60%, 96%, and 94%, respectively. However, the blunted pattern had low sensitivity (22%), specificity (61%), and predictive values (30%) for detecting ROA of greater than 0.3 cm2 with significant overlap with the reversed and normal patterns. Among patients with the blunted pattern, the correlation between the systolic to diastolic velocity ratio was worse in those with LV dysfunction (ejection fraction <50%, r = 0.23, P > .05) than in those with normal LV function (r = –0.57, P < .05). Stepwise linear regression analysis showed that the peak systolic to diastolic velocity ratio was independently correlated with RF (P < .001) and effective stroke volume (P < .01), with a multiple correlation coefficient of 0.71 (P < .001). In conclusion, reversed pulmonary venous flow in systole is a highly specific and reliable marker of moderately severe or severe MR with an ROA greater than 0.3 cm2, whereas the normal pattern accurately predicts mild to moderate MR. Blunted pulmonary venous flow can be seen in all grades of MR with low predictive value for severity of MR, especially in the presence of LV dysfunction. The blunted pulmonary venous flow pattern must therefore be interpreted cautiously in clinical practice as a marker for severity of MR. (J Am Soc Echocardiogr 1999;12:736-43.)

BACKGROUND:The effective orifice area (EOA) of a prosthetic valve is superior to transvalvular gradients as a measure of valve function, but measurement of mitral prosthesis EOA has not been reliable.METHODS AND RESULTS:In vitro flow across St Jude valves was calculated by hemispheric proximal isovelocity surface area (PISA) and segment-of-spheroid (SOS) methods. For steady and pulsatile conditions, PISA and SOS flows correlated with true flow, but SOS and not PISA underestimated flow. These principles were then used intraoperatively to calculate cardiac output and EOA of newly implanted St Jude mitral valves in 36 patients. Cardiac output by PISA agreed closely with thermodilution (r=0.91, Delta=-0.05+/-0.55 L/min), but SOS underestimated it (r=0.82, Delta=-1.33+/-0.73 L/min). Doppler EOAs correlated with Gorlin equation estimates (r=0.75 for PISA and r=0.68 for SOS, P<0.001) but were smaller than corresponding in vitro EOA estimates.CONCLUSIONS:Proximal flow convergence methods can calculate forward flow and estimate EOA of St Jude mitral valves, which may improve noninvasive assessment of prosthetic mitral valve obstruction.

Objectives. We studied the effects of left ventricular (LV) unloading by an implantable ventricular assist device on LV diastolic filling.Background. Although many investigators have reported reliable systemic and peripheral circulatory support with implantable LV assist devices, little is known about their effect on cardiac performance,Methods. Peak velocities of early diastolic filling, late diastolic filling, late to early filling ratio, deceleration time of early filling, diastolic filling period and atrial filling fraction were measured by intraoperative transesophageal Doppler echocardiography before and after insertion of an LV assist device in eight patients. A numerical model was developed to simulate this situation,Results. Before device insertion, all patients showed either a restrictive or a monophasic transmitral flow pattern, After device insertion, transmitral flow showed rapid beat to beat variation in each patient, from abnormal relaxation to restrictive patterns, However, when the average values obtained from 10 consecutive beats were considered, overall filling was significantly normalized from baseline, with early filling velocity falling front 87 +/- 31 to 64 +/- 26 cm/s (p < 0.01) and late filling velocity rising from 8 +/- 11 to 32 +/- 23 cm/s (p < 0.05), resulting in an increase in the late to early filling ratio from 0.13 +/- 0.18 to 0.59 +/- 0.38 (p < 0.01) and a rise in the atrial filling fraction from 8 +/- 10% to 26 +/- 17% (p < 0.01). The deceleration time (from 112 +/- 40 to 160 +/- 44 ms, p < 0.05) and the filling period corrected by the RX interval (from 39 +/- 8% to 54 +/- 10%, p < 0.005) were also significantly prolonged. In the computer model, asynchronous LV assistance produced significant beat to beat variation in filling indexes, but overall a normalization of deceleration time as well as other variables.Conclusions. With LV assistance, transmitral flow showed rapidly varying patterns beat by beat in each patient, but overall diastolic filling tended to normalize with an increase of atrial contribution to the filling, Because of the variable nature of the transmitral flow pattern with the assist device, the timing of the device cycle must be considered when inferring diastolic function from transmitral flow pattern, (C) 1997 by the American College of Cardiology.

To study the physical and physiological determinants of transmitral and pulmonary venous flow, a lumped-parameter model of the cardiovascular system has been created, modeling the instantaneous pressure, volume, and influx/efflux of the pulmonary veins, left atrium and ventricle, systemic arteries and veins. right atrium and ventricle, and pulmonary arteries. Initial validation has been obtained by direct comparison with transesophageal echocardiographic recordings of mitral and pulmonary venous velocity for the following clinical situations: normal diastolic function, delayed ventricular relaxation, restrictive filling due to severe systolic dysfunction, severe mitral regurgitation before and after valve repair surgery, and premature atrial contraction occurring during ventricular systole. Sensitivity analysis has been performed with a Jacobian matrix, representing the proportional change in a group of output indexes (yi) in response to isolated changes in input parameters (xj), [(delta yi/yi)/ ([delta xj/xj)], demonstrating the complementary nature of mitral and pulmonary venous A-wave velocity for predicting ventricular stiffness and atrial systolic function. This unified numerical-experimental programming environment should facilitate model refinement and physiological data exploration, in particular guiding more accurate interpretations of Doppler echocardiographic data.

Color Doppler M-mode echocardiographic imaging has been shown to provide useful information in the evaluation of left ventricular diastolic filling and function. However, descriptors of the spatiotemporal velocity inflow pattern do not take advantage of the full digital velocity map and are not available in an automated fashion. The purpose of this study was to automate the quantification of flow propagation features and evaluate their ability to assess diastolic filling abnormalities. Isovelocity contouring and gradient analysis were applied to identify features of the early filling wave. These feature parameters were compared in normal and diastolic dysfunction patient groups (N=20). Several features allowed classification of the two patient groups with sensitivity and specificity greater than 80%. This automated process may allow these features to be obtained on a regular basis and provide information for diagnosis and assessment of diastolic dysfunction.