Physiology of diastolic function and transmitral pressure-flow relations.

The study of diastolic function, in particular, the creative application of noninvasive modalities, such as echocardiography and MR imaging, requires an understanding and appreciation of the basic physiology of left ventricular filling dynamics. The physics and physiology of diastolic function and dysfunction is examined by relating the phasic patterns of transmitral flow to the properties of the cardiac chambers. Particular attention is paid to the equations governing the transmitral pressure-flow relations and the active and passive chamber properties that determine the flow patterns: Active relaxation, passive compliance, viscoelasticity, and elastic deformation. The physiologic role of diastolic suction is discussed within this context.

Modeling of diastole.

Modeling methods have been employed to further characterize the physical and physiologic processes of filling and diastolic function. They have led to more detailed understanding of the effect of alteration of physiologic parameters on the Doppler E-wave contour as well as pulmonary vein flow. Depending on the modeling approach, different aspects of the filling process have been considered from AV gradient and net compliance to atrial appendage function to the mechanical suction pump attribute of the heart. The models have been applied for further characterization of diastolic function and elucidation of novel basic physiologic relations. We trust that readers recognize that this article could not serve as a comprehensive and global review of the state-of-the-art in physiologic modeling, but rather as a selective overview, with emphasis on the main modeling principles and options currently in use. Modeling of systems physiology, especially as it relates to the function of the four-chamber heart, remains a fertile area of investigation. Future progress is likely to have profound influence on (noninvasive) diagnosis and quantitation of the effect of therapy and lead to continued discovery of "new" (macroscopic, cellular, and molecular biologic) physiology.

Simultaneous Doppler/catheter measurements of pressure gradients in aortic valve disease: a correction to the Bernoulli equation based on velocity decay in the stenotic jet.

BACKGROUND AND AIM OF THE STUDY: Characterization of the severity of a stenotic aortic valve relies on accurate measurement of the pressure drop across the valve. A simplified form of the Bernoulli equation has been used to estimate pressure drops using Doppler ultrasound, but these measurements often overestimate gold standard measurements performed during cardiac catheterization. Sources of discrepancy between the Doppler and catheter measurements have been identified, but no method has been developed to fully reconcile the two techniques. METHODS: In this study we developed a correction to the clinical form of the Bernoulli equation based on receiving chamber geometry and turbulent jet profiles. The theoretical treatment of the mechanical energy balance, assuming a shape to the stenotic jet profile is described, and the assumptions in our model are discussed. The use of the model was then demonstrated in an in vivo clinical study in which simultaneous Doppler and catheter data were obtained. RESULTS: Discrepancies between Doppler and catheter are shown to be a function of the predicted pressure recovery location based on our assumed profile. There exists a distance of about 8.67 valve radii downstream where agreement in peak pressure gradients is theoretically achieved. CONCLUSION: The results demonstrate the ability to characterize pressure recovery distal to the valve. Our approach, to substitute a more appropriate velocity profile into the mechanical energy balance, unifies geometric parameters and the physics of turbulent jet flow in an equation involving quantities already routinely measured in an echocardiographic examination of aortic stenosis. This allows for both the maximal and recovered pressure gradient to be obtained from the Doppler data. These results have implications for optimal pressure sensor placement for the assessment of aortic stenosis and also for the evaluation of prosthetic heart valves in vitro.

Clinical significance of fossa ovalis membrane aneurysm in adults with cardioembolic cerebral ischemia.

Fossa ovalis membrane aneurysm was diagnosed by transesophageal echocardiography in 45 of 134 consecutive patients (34%) with embolic cerebrovascular ischemic events. A potential cardiovascular source of embolism, other than the fossa ovalis membrane aneurysm, was found in 91% of these patients (41 of 45).

Improved Doppler echocardiographic assessment of the left atrial appendage by peripheral vein injection of sonicated albumin microbubbles.

We evaluated the usefulness of peripherally injected sonicated albumin microbubbles in transesophageal echo-Doppler cardiographic assessment of the left atrial appendage in 19 patients (age 61 +/- 19 [range 21 to 86] years; 12 [63%] women). Multiplane transesophageal echocardiography was performed before and after intravenous injection of sonicated albumin, and the left atrial appendage image and Doppler flow signal quality were assessed by a grading system of 0 to 3+ (0 = poor, 1 + = adequate, 2+ = good, and 3+ = excellent). Microbubbles appeared in the left atrium in 15 (79%) of 19 patients and completely opacified the left atrial appendage in 7 (37%) of 19 patients. Left atrial appendage maximal and minimal areas by planimetry were similar before and after contrast injection, although image quality improved in 13 (68%) of 19 patients (echocardiographic grade 1.8 +/- 0.6 vs 2.6 +/- 0.5, p< 0.001). Similarly, left atrial appendage peak emptying and peak filling Doppler flow velocities did not change before and after contrast injection, although Doppler flow signal quality improved in 12 (63%) of 19 patients (Doppler grade 1.6 +/- 0.5 vs 2.1 +/- 0.8, p < 0.05). Overall, contrast injection improved left atrial appendage echocardiographic or Doppler quality in 16 (84%) of 19 patients. Thus peripheral vein injection of sonicated albumin microbubbles can improve the assessment of left atrial appendage structure and function by transesophageal echocardiography.

Atrial contribution to ventricular filling in mitral stenosis.

BACKGROUND: The importance of the contribution of atrial systole to ventricular filling in mitral stenosis is controversial. The cause of reduced cardiac output following the onset of atrial fibrillation may be due to an increased heart rate, a loss of booster pump function, or both. METHODS AND RESULTS: We studied the atrial contribution to filling under a variety of conditions by combining noninvasive studies of patients with computer modeling. Thirty patients in sinus rhythm with mild-to-severe stenosis were studied with two-dimensional and Doppler echocardiography for measurement of mitral flow velocity and mitral valve area (MVA). The mean +/- SD atrial contribution to left ventricular filling volume was 18 +/- 10% and varied inversely with mitral resistance. Patients with mild mitral stenosis (MVA, 1.8 +/- 0.7 cm2) and severe mitral stenosis (MVA, 0.9 +/- 0.2 cm2) had atrial contributions of 29 +/- 4% and 9 +/- 5%, respectively. The pathophysiological mechanisms responsible for these trends were further investigated by the computer model. In modeled severe mitral stenosis, increasing heart rate from 75 to 150 beats/min caused an increase of 5.2 mm Hg in mean left atrial pressure, whereas loss of atrial contraction at a heart rate of 150 beats/min caused only a 1.3 mm Hg increase. CONCLUSIONS: The atrial booster pump contributes less to ventricular filling in mitral stenosis than in the normal heart, and the loss of atrial pump function is less important than the effect of increasing heart rate as the cause of decompensation during atrial fibrillation.

Passive properties of canine left ventricle: diastolic stiffness and restoring forces.

Left ventricular (LV) diastolic pressure-volume (P-V) relations arise from a complex interplay of active decay of force (i.e., relaxation), passive elastic myocardial properties, and time-varying inflow across the mitral orifice. This study was designed to quantify the passive properties of the intact ventricle and the effects of elastic recoil by separating filling from relaxation with a method of LV volume clamping with a remote-controlled mitral valve. Eleven open-chest fentanyl-anesthetized dogs were instrumented with aortic and mitral flow probes, LV and left atrium micromanometers, and a remote-controlled mitral valve. We prevented complete (end-systolic volume clamping) or partial filling at different times in diastole. The ventricle thus relaxed completely at different volumes, and we generated P-V coordinates for the passive ventricle that included negative, as well as positive, values of pressure. We then estimated ventricular volumes from ventricular weight in eight dogs, using regression equations based on data in the literature, to determine the equilibrium volume (V0), that is, volume at zero transmural pressure, in the working ventricle. We abandoned the traditional exponential approach and characterized by the P-V relation with a logarithmic approach that included maximum LV volume (Vm), minimum volume (Vd), and stiffness parameters (Sp and Sn) for the positive (p) and negative (n) phases: Pp = -Sp In[(Vm - V)/(Vm - V0)] and Pn = Sn In[(V - Vd)/(V0 - Vd)]. With this formulation, the chamber compliance, dP/dV, is normalized by the LV operating volume, and Sp and Sn are size-independent chamber stiffness parameters with the units of stress. In eight ventricles with LV weight = 131 +/- 20 g, Vm = 116 +/- 18 ml, V0 = 37 +/- 6 ml, and Vd = 13 +/- 2 ml, stiffness Sp = 14.6 mm Hg and Sn = 5.1 mm Hg were determined from the slopes of the log-linearized equations. Also, the duration of LV relaxation is increased by the process of ventricular filling (161 +/- 31 msec, filling versus 108 +/- 36 msec, nonfilling, measured from dP/dtmin, p less than 0.0001). We conclude that volume clamping is a useful method of studying restoring forces and that the logarithmic approach is conceptually and quantitatively useful in characterizing the passive properties of the intact ventricle.

Time variation of mitral regurgitant flow in patients with dilated cardiomyopathy.

Angiographic results in patients with mitral regurgitation suggest that up to 50% of the regurgitant volume occurs during the preejection period. This contrasts markedly with the electromagnetic measurements of mitral regurgitant flow in anesthetized dogs, which suggest that only 5% of mitral regurgitant flow occurs during the preejection period. Therefore, we used two-dimensional and Doppler echocardiography to quantify mitral regurgitation during aortic ejection and in the preejection and postejection periods in eight patients with severe heart failure. Mitral regurgitant volume (RV) was calculated as the difference between total stroke volume (by two-dimensional echocardiography) and forward aortic flow (by pulsed Doppler). Regurgitant velocity (V) and time (RT) were measured by continuous-wave Doppler, and the mean regurgitant area (RAm) was calculated from the RT and mean regurgitant velocity (Vm): RAm = (RV/RT)/Vm. As a first approximation, the RA was assumed to be constant during systole, and the regurgitant volume during aortic ejection and during the preejection and postejection periods was calculated from: RVi = (Vmi) (RTi) (TAm), where Ti represents the duration of the appropriate period. Percentages of total regurgitant volume occurring during the preejection, ejection, and postejection periods were 13 +/- 4%, 79 +/- 5%, and 8 +/- 5%, respectively. Thus, in contrast to previously reported angiographic studies, mitral regurgitation occurs predominantly during the aortic ejection period. These results were not substantially changed by assuming a 20% reduction in effective regurgitant orifice area between the preejection and ejection periods and are consistent with data from chronically instrumented dogs with mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure.

Peak rapid filling rate (PRFR) is often used clinically as an index of left ventricular relaxation, i.e., of early diastolic function. This study tests the hypothesis that early filling rate is a function of the atrioventricular pressure difference and hence is influenced by the left atrial pressure as well as by the rate of left ventricular relaxation. As indexes, we chose the left atrial pressure at the atrioventricular pressure crossover (PCO), and the time constant (T) of an assumed exponential decline in left ventricular pressure. We accurately determined the magnitude and timing of filling parameters in conscious dogs by direct measurement of phasic mitral flow (electromagnetically) and high-fidelity chamber pressures. To obtain a diverse hemodynamic data base, loading conditions were changed by infusions of volume and angiotensin II. The latter was administered to produce a change in left ventricular pressure of less than 35% (A-1) or a change in peak left ventricular pressure of greater than 35% (A-2). PRFR increased with volume loading, was unchanged with A-1, and was decreased with A-2; T and PCO increased in all three groups (p less than .005 for all changes). PRFR correlated strongly with the diastolic atrioventricular pressure difference at the time of PRFR (r = .899, p less than .001) and weakly with both T (r = .369, p less than .01) and PCO (r = .601, p less than .001). The correlation improved significantly when T and PCO were both included in the multivariate regression (r = .797, p less than .0001). PRFR is thus determined by both the left atrial pressure and the left ventricular relaxation rate and should be used with caution as an index of left ventricular diastolic function.

Interrelationship of mid-diastolic mitral valve motion, pulmonary venous flow, and transmitral flow.

This study offers a unifying mechanism of left ventricular filling dynamics to link the unexplained mid-diastolic motion of the mitral valve with an associated increase in transmitral flow, with the phasic character of pulmonary vein flow, and with changes in the atrioventricular pressure difference. M mode echograms of mitral valve motion and Doppler echocardiograms of mitral and pulmonary vein flow velocities were recorded in 12 healthy volunteers (heart rate = 60 +/- 9 beats/min). All echocardiograms showed an undulation in the mitral valve (L motion) at a relatively constant delay from the peak of the diastolic phase of pulmonary vein flow (K phase). In six subjects, the L motion was also associated with a distinct wave of mitral flow (L wave). Measured from the onset of the QRS complex, Q-K was 577 +/- 39 msec; Q-L was 703 +/- 42 msec, and K-L was 125 +/- 16 msec. Multiple measurements within each subject during respiratory variations in RR interval indicated exceptionally small differences in the temporal relationships (mean coefficient of variation 2%). Early rapid flow deceleration is caused by a reversal of the atrioventricular pressure gradient, and the L wave arises from the subsequent reestablishment of a positive gradient due to left atrial filling via the pulmonary veins. The mitral valve moves passively in response to the flowing blood and the associated pressure difference. This interpretation is confirmed by (1) a computational model, and (2) a retrospective analysis of data from patients with mitral stenosis and from conscious dogs instrumented to measure transmitral pressure-flow relationships.

Development and use of a remote-controlled mitral valve.

A remote-controlled mitral valve was designed and constructed to occlude the mitral or tricuspid orifice at any time in the cardiac cycle. It is used to study ventricular properties in the anesthetized dog by controlling ventricular filling, atrial properties by controlling atrial emptying and interaction of the two chambers by uncoupling them. The device can produce transient or steady-state perturbations in filling volume which make possible studies of intrinsic control of cardiac output. When filling volume is transiently reduced, stroke volume and end-systolic volume are reduced. A compensatory increase in stroke volume of the next cycles occurs due to increased ventricular preload and reduced afterload. The compensation continues until the lost stroke volume is regained, at which time the system returns to its previous steady state.

Effects of timing of atrial systole on LV filling and mitral valve closure: computer and dog studies.

Atrioventricular (AV) delay that results in maximum ventricular filling and physiological mechanisms that govern dependence of filling on timing of atrial systole were studied by combining computer experiments with experiments in the anesthetized dog instrumented to measure phasic mitral flow. Ventricular filling volume is maximized at AV delay of 100 ms in the computer study and 80 ms in the dog study. At any time in diastole atrial contraction accelerates mitral flow, opening the mitral valve widely; atrial relaxation then decelerates mitral flow, moving the valve leaflets toward closure. The time the valve remains closed following atrial systole varies inversely with AV delay. When AV delay is optimal, the mitral valve is moving rapidly toward closure but is not yet closed at onset of ventricular systole. The decline in filling volume as AV delay decreases below its optimum value is primarily the result of premature termination of atrial ejection by ventricular systole. As AV delay increases above its optimal value, filling volume progressively decreases because of premature mitral valve closure that limits effective diastolic filling period. There is no significant retrograde mitral flow at any point in diastole for any AV delay.