Physiologic determinants of mitral inflow pattern using a computer simulation: insights into Doppler echocardiography in diverse phenotypes.

BACKGROUND: Although echo Doppler recordings of mitral inflow patterns are often employed clinically to identify "diastolic dysfunction," abnormal flow profiles may be seen in a diverse set of disorders in which the specific physiologic determinants are not well defined. METHODS: We used a validated cardiovascular simulation model to assess the effects of four hemodynamic parameters on Doppler measures of LV filling: (1) total blood volume, (2) diastolic stiffness (LV Beta), (3) systemic vascular resistance (SVR), and (4) pulmonary vascular resistance (PVR). In each simulation, we calculated instantaneous flow through the mitral valve as a function of time. RESULTS: Increases in blood volume led to an increase in the E:A ratio and a decrease in deceleration time (DT), such that for every 100 mL of volume, DT decreased by approximately 3 ms. Increases in LV Beta increased the E:A ratio and decreased DT such that for every 0.005 mmHg/mL increase in LV Beta, DT decreased by approximately 8 ms. While changes in SVR did not significantly alter the Doppler pattern, increases in PVR effected a prolongation of DT and an impaired relaxation E:A pattern. Increasing blood volume and LV Beta simultaneously was additive, while increasing PVR attenuated the effect of increasing volume on the E:A ratio. CONCLUSIONS: Computer simulations demonstrate that both blood volume and LV stiffness significantly impact the mitral inflow profile indicating that both filling pressure and intrinsic properties of the ventricle are contributors. These data confirm that there are multiple determinants of the Doppler mitral inflow pattern and suggest a new approach toward understanding complex physiologic interactions.

Hemodynamic effects of partial ventricular support in chronic heart failure: results of simulation validated with in vivo data.

OBJECTIVE: Current left ventricular assist devices are designed to provide full hemodynamic support for patients with end-stage failing hearts, but their use has been limited by operative risks, low reliability, and device-related morbidity. Such concerns have resulted in minimum use of left ventricular assist devices for destination therapy. We hypothesize that partial circulatory support, which could be achieved with small pumps implanted with less-invasive procedures, might expand the role of circulatory support devices for treatment of heart failure. METHODS: We examine the hemodynamic effects of partial left ventricular support using a previously described computational model of the cardiovascular system. Results from simulations were validated by comparison with an in vivo hemodynamic study. RESULTS: Simulations demonstrated that partial support (2-3 L/min) increased total cardiac output (left ventricular assist device output plus native heart output) by more than 1 L/min and decreased left ventricular end-diastolic pressure by 7 to 10 mm Hg with moderate-to-severe heart failure. Analyses showed that the hemodynamic benefits of increased cardiac output and decreased left ventricular end-diastolic pressure are greater in less-dilated and less-dysfunctional hearts. Both the relationships between ventricular assist device flow and cardiac output and ventricular assist device flow and left atrial pressure predicted by the model closely approximated the same relationships obtained during hemodynamic study in a bovine heart failure model. CONCLUSIONS: Results suggest that a pump with a flow rate of 2 to 3 L/min could meaningfully affect cardiac output and blood pressure in patients with advanced compensated heart failure. The development of small devices capable of high reliability and minimal complications that can be implanted with less-invasive techniques is supported by these findings.

Role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure.

Although present in many patients with heart failure and a normal ejection fraction, the role of isolated impairments in active myocardial relaxation in the genesis of elevated filling pressures is not well characterized. Because of difficulties in determining the effect of prolonged myocardial relaxation in vivo, we used a cardiovascular simulated computer model. The effect of myocardial relaxation, as assessed by tau (exponential time constant of relaxation), on pulmonary vein pressure (PVP) and left ventricular end-diastolic pressure (LVEDP) was investigated over a wide range of tau values (20-100 ms) and heart rate (60-140 beats/min) while keeping end-diastolic volume constant. Cardiac output was recorded over a wide range of tau and heart rate while keeping PVP constant. The effect of systolic intervals was investigated by changing time to end systole at the same heart rate. At a heart rate of 60 beats/min, increases in tau from a baseline to extreme value of 100 ms cause only a minor increase in PVP of 3 mmHg. In contrast, at 120 beats/min, the same increase in tau increases PVP by 23 mmHg. An increase in filling pressures at high heart rates was attributable to incomplete relaxation. The PVP-LVEDP gradient was not constant and increased with increasing tau and heart rate. Prolonged systolic intervals augmented the effects of tau on PVP. Impaired myocardial relaxation is an important determinant of PVP and cardiac output only during rapid heart rate and especially when combined with prolonged systolic intervals. These findings clarify the role of myocardial relaxation in the pathogenesis of elevated filling pressures characteristic of heart failure.