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In the recently published clinical study [Use of Nitroprusside in Left Ventricular Dysfunction and Obstructive Aortic Valve Disease (UNLOAD)], sodium nitroprusside (SNP) improved cardiac function in patients with severe aortic stenosis (AS) and left ventricular (LV) systolic dysfunction. We explored the possible mechanisms of these findings using a series of numerical simulations. A closed-loop lumped parameters model that consists of 24 differential equations relating pressure and flow throughout the circulation was used to analyze the effects of varying hemodynamic conditions in AS. Hemodynamic data from UNLOAD study subjects were used to construct the initial simulation. Systemic vascular resistance (SVR), heart rate, and aortic valve area were directly entered into the model while end-systolic and end-diastolic pressure-volume (P-V) relationships were adjusted using previously published data to match modeled and observed end-systolic and end-diastolic pressures and volumes. Initial simulation of SNP treatment by a reduction of SVR was not adequate. To obtain realistic model hemodynamics that reliably reproduce SNP treatment effects, we performed a series of simulations while simultaneously changing end-systolic elastance ([E.sub.es]), end-systolic volume at zero pressure (Vo). and diastolic P-V shift. Our data indicate that either an [E.sub.es] increase or [V.sub.o] decrease is necessary to obtain realistic model hemodynamics. In five patients, we corroborated our findings by using the model to duplicate individual P-V loops obtained before and during SNP treatment. In conclusion, using a numerical model, we identified ventricular function parameters that are responsible for improved hemodynamics during SNP infusion in AS with LV dysfunction. ventricular mechanics; contractility; afterload

Coupled pacing improves cardiac efficiency during acute atrial fibrillation with or without cardiac dysfunction. Am J Physiol Heart Circ Physiol 287: H2016-H2022, 2004. First published July 29, 2004; doi:10.1152/ajpheart.00347.2004.--Coupled pacing (CP), a method for controlling ventricular rate during atrial fibrillation (AF), consists of a single electrical stimulation applied to the ventricles after each spontaneous activation. CP results in a mechanical contraction rate approximately one-half the rate during AF. Paired stimulation in which two electrical stimuli are delivered to the ventricles has also been proposed as a therapy for heart failure. Although paired stimulation enhances contractility, it greatly increases energy consumption. The primary hypothesis of the present study is that CP improves cardiac function during acute AF without a similar increase in energy consumption because of the reduced rate of ventricular contractions. In a canine model, CP was applied during four stages: sinus rhythm (SR), acute AF, cardiac dysfunction (CD), and AF in the presence of cardiac dysfunction. The rate of ventricular contraction decreased in all four stages as the result of CP. In addition, we determined the changes in external cardiac work, myocardial oxygen consumption, and myocardial efficiency in the each of tour stages. CP partially reversed the effects of AF and CD on external cardiac work, whereas myocardial oxygen consumption increased only moderately. In all stages but SR, CP increased myocardial efficiency because of the marked increases in cardiac work compared with the moderate increases in total energy consumed. Thus this pacing therapy may be a viable therapy for patients with concurrent atrial fibrillation and heart failure. heart failure; rate control; external cardiac work: oxygen consumption

Preload-adjusted right ventricular maximal power: concept and validation. Am J Physiol Heart Circ Physio1287: H1632-H1640, 2004. First published May 20, 2004; 10.1152/ajpheart.00123.2004.-Right ventricular (RV) maximal power (PW[R.sub.mx]) is dependent on preload. The objective of this study was to test our hypothesis that the PW[R.sub.mx] versus end-diastolic volume (EDV) relationship, analogous to the load-independent stroke work (SW) versus EDV relationship (preload-recruitable SW, PRSW), is linear, with the PWR x-axis intercept ([V.sub.OPWR]) corresponding to the PRSW intercept ([V.sub.OSW]). If our hypothesis is correct, the preload sensitivity of PW[R.sub.mx] could be eliminated by adjusting for EDV and [V.sub.OPWR]. Ten dogs were instrumented with a pulmonary flow probe, micromanometers, and RV conductance catheter. Data were obtained during bicaval occlusions under various conditions and fitted to [PWR.sub.mx] = a * [(EDV - [V.sub.OPWR]).sup.[beta]], where a is the slope of the relationship. The PW[R.sub.mx] versus EDV relationship did not deviate from linearity ([beta] = 1.09, P = not significant vs. 1), and [V.sub.OPWR] correlated with [V.sub.OSW] (r - 0.93, P hemodynamics; contractility; right ventricle

Stress echocardiography is a routinely used clinical procedure to diagnose cardiac dysfunction by comparing wall motion information in prestress and poststress ultrasound images. Incomplete data, complicated imaging protocols and misaligned prestress and poststress views, however, are known limitations of conventional stress echocardiography. We discuss how the first two limitations are overcome via the use of real-time three-dimensional (3-D) ultrasound imaging, an emerging modality, and have called the new procedure '3-D stress echocardiography.' We also show that the problem of misaligned views can he solved by registration of prestress and poststress 3-D image sequences. Such images are misaligned because of variations in placing the ultrasound transducer and stress-induced anatomical changes. We have developed a technique to temporally align 3-D images of the two sequences first and then to spatially register them to rectify probe placement error while preserving the stress-induced changes. The 3-D spatial registration is mutual information-based. Image registration used in conjunction with 3-D stress echocardiography can potentially improve the diagnostic accuracy of stress testing. Index Terms--Image registration, mutual information, stress echocardiography, three-dimensional ultrasound imaging.

Doppler-derived gradients may overestimate total pressure loss in degenerative and prosthetic aortic valve stenosis (AS) due to unaccounted pressure recovery distal to the orifice. However, in congenitally bicuspid valves, jet eccentricity may result in a higher anatomic-to-effective orifice contraction ratio, resulting in an increased pressure loss at the valve and a reduced pressure recovery distal to the orifice leading to greater functional severity. The objective of our study was to determine the impact of local geometry on the total versus Doppler-derived pressure loss and therefore the assessed severity of the stenosis in bicuspid valves. On the basis of clinically obtained measurements, two- and three-dimensional computer simulations were created with various local geometries by altering the diameters of the left ventricular outflow tract (LVOT; 1.8-3.0 cm), orifice diameter (OD; 0.8-1.6 cm), and aortic root diameter (AR; 3.0-5.4 cm). Jet eccentricity was altered in the models from 0 to 25[degrees]. Simulations were performed under steady-flow conditions. Axisymmetric simulations indicate that the overall differences in pressure recovery were minor for variations in LVOT diameter ( Doppler; echocardiography; congenital heart disease

Left ventricular (LV) diastolic function during atrial fibrillation (AF) remains poorly understood due to the complex interaction of factors and beat-to-beat variability. The purpose of the present study was to elucidate the physiological determinants of beat-to-beat changes in LV diastolic function during AF. The RR intervals preceding a given cardiac beat were measured from the right ventricular electrogram in 12 healthy open-chest mongrel dogs during AF. Doppler echocardiography and LV pressure and volume beat-to-beat analyses were performed. The LV filling time (FT) and early diastolic mitral inflow velocity-time integral ([E.sub.vti]) were measured using the pulsed Doppler method. The LV end-diastolic volume (EDV), peak systolic LV pressure (LVP), minimum value of the first derivative of LV pressure curve (dP/[dt.sub.min]), and the time constant of LV pressure decay ([tau]) were evaluated with the use of a conductance catheter for 100 consecutive cardiac cycles. Beat-to-beat analysis revealed a cascade of important causal relations. LV-FT showed a significant positive linear relationship with [E.sub.vti] (r = 0.87). Importantly, there was a significant positive linear relationship between the RR interval and LV-EDV in the same cardiac beat (r = 0.53). Consequently, there was a positive linear relationship between LV-EDV and subsequent peak systolic LVP (r = 0.82). Furthermore, there were significant positive linear and negative curvilinear relationships between peak systolic LVP and dP/[dt.sub.min] (r = 0.95) and [tau] (r = -0.85), respectively, in the same cardiac beat. In addition, there was a significant negative curvilinear relationship between dP/[dt.sub.min] and [tau] (r = -0.86). We have concluded that the determinants of LV diastolic function in individual beats during AF depend strongly on the peak systolic LVP. This suggests that the major benefit of slower ventricular rate appears related to lengthening of LV filling interval, promoting subsequent higher peak systolic LVP and greater LV relaxation. filling interval; left ventricular pressure

We sought to validate measurement of intraventricular pressure gradients (IVPG) and analyze their change in patients with hypertrophic obstructive cardiomyopathy (HOCM) after ethanol septal reduction (ESR). Quantitative analysis of color M-mode Doppler (CMM) images may be used to estimate diastolic IVPG noninvasively. Noninvasive IVPG measurement was validated in 10 patients undergoing surgical myectomy. Echocardiograms were then analyzed in 19 patients at baseline and after ESR. Pulsed Doppler data through the mitral valve and pulmonary venous flow were obtained. CMM was used to obtain the flow propagation velocity ([V.sub.p]) and to calculate IVPG off-line. Left atrial pressure was estimated with the use of previously validated Doppler equations. Data were compared before and after ESR. CMM-derived IVPG correlated well with invasive measurements obtained before and after surgical myectomy [r = 0.8, P < 0.01, [DELTA](CMM--invasive IVPG) = 0.09 [+ or -] 0.45 mmHg]. ESR resulted in a decrease of resting LVOT systolic gradient from 62 [+ or -] 10 to 29 [+ or -] 5 mmHg (P < 0.001). There was a significant increase in the [V.sub.p] and IVPG (from 48 [+ or -] 5 to 74 [+ or -] 7 cm/s and from 1.5 [+ or -] 0.2 to 2.6 [+ or -] 0.3 mmHg, respectively, P < 0.001 for both). Estimated left atrial pressure decreased from 16.2 [+ or -] 1.1 to 11.5 [+ or -] 0.9 mmHg (P < 0.001). The increase in IVPG correlated with the reduction in the LVOT gradient (r = 0.6, P < 0.01). Reduction of LVOT obstruction after ESR is associated with an improvement in diastolic suction force. Noninvasive measurements of IVPG may be used as an indicator of diastolic function improvement in HOCM. echocardiography; diastolic function; hypertrophic obstructive cardiomyopathy

The drug nitroprusside may improve heart function in patients with severe aortic stenosis and heart failure while they wait for an aortic valve replacement, according to a study of 25 patients. Aortic stenosis occurs when the aortic valve in the heart becomes stiff and no longer functions properly. Nitroprusside belongs to a group of drugs called vasodilators because they dilate blood vessels.

Previous echocardiographic techniques for quantifying valvular regurgitation (PISA) are limited by factors including uncertainties in orifice location and hemispheric convergence assumption. Using computational fluid dynamics simulations, we developed a new model for the estimation of orifice diameter and regurgitant volume without the aforementioned assumptions of the PISA technique. Using experimental data obtained from the in vitro flow model we successfully validated our new model. The model output (y) and reference (x) values were in close agreement (y=0.95x +0.38, r=0.96, error=1.68 [+ or -] 7.54% for the orifice diameter and y=1.18x -4.72, r=0.93, error=6.48 [+ or -] 16.81% for the regurgitant volume).

Purpose: The purpose of this study was to evaluate the accuracy of four‐dimensional (4D) flow MRI for direct assessment of peak velocity, flow volume, and momentum of a mitral regurgitation (MR) flow jets using an in vitro pulsatile jet flow phantom. We systematically investigated the impact of spatial resolution and quantification location along the jet on flow quantities with Doppler ultrasound as a reference for peak velocity. Methods: Four‐dimensional flow MRI data of a pulsatile jet through a circular, elliptical, and 3D‐printed patient‐specific MR orifice model was acquired with varying spatial resolution (1.5–5 mm isotropic voxel). Flow rate and momentum of the jet were quantified at various axial distances (x = 0–50 mm) and integrated over time to calculate Voljet and MTIjet. In vivo assessment of Voljet and MTIjet was performed on 3 MR patients. Results: Peak velocities were comparable to Doppler ultrasound (3% error, 1.5 mm voxel), but underestimated with decreasing spatial resolution (−40% error, 5 mm voxel). Voljet was similar to regurgitant volume (RVol) within 5 mm, and then increased linearly with the axial distance (19%/cm) because of flow entrainment. MTIjet remained steady throughout the jet (2%/cm) as theoretically predicted. Four and 9 voxels across the jet were required to measure flow volume and momentum‐time‐integral within 10% error, respectively. Conclusion: Four‐dimensional flow MRI detected accurate peak velocity, flow rate, and momentum for in vitro MR‐mimicking flow jets. Spatial resolution significantly impacted flow quantitation, which otherwise followed predictions of flow entrainment and momentum conservation. This study provides important preliminary information for accurate in vivo MR assessment using 4D flow MRI. [ABSTRACT FROM AUTHOR]