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Modeling left ventricular diastolic dysfunction: classification and key indicators.

Luo C, Ramachandran D, Ware DL, Ma TS, Clark JW - Theor Biol Med Model (2011)

Bottom Line: The effects of increasing systolic contractility are also considered.IR-type decreases, but R-type increases the mitral E/A ratio.The model demonstrates that abnormal LV diastolic performance alone can result in decreased LV and RV systolic performance, not previously appreciated, and contribute to the clinical syndrome of HF.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept, Electrical and Computer Engineering, Rice University, Houston, TX 77005, USA.

ABSTRACT

Background: Mathematical modeling can be employed to overcome the practical difficulty of isolating the mechanisms responsible for clinical heart failure in the setting of normal left ventricular ejection fraction (HFNEF). In a human cardiovascular respiratory system (H-CRS) model we introduce three cases of left ventricular diastolic dysfunction (LVDD): (1) impaired left ventricular active relaxation (IR-type); (2) increased passive stiffness (restrictive or R-type); and (3) the combination of both (pseudo-normal or PN-type), to produce HFNEF. The effects of increasing systolic contractility are also considered. Model results showing ensuing heart failure and mechanisms involved are reported.

Methods: We employ our previously described H-CRS model with modified pulmonary compliances to better mimic normal pulmonary blood distribution. IR-type is modeled by changing the activation function of the left ventricle (LV), and R-type by increasing diastolic stiffness of the LV wall and septum. A 5th-order Cash-Karp Runge-Kutta numerical integration method solves the model differential equations.

Results: IR-type and R-type decrease LV stroke volume, cardiac output, ejection fraction (EF), and mean systemic arterial pressure. Heart rate, pulmonary pressures, pulmonary volumes, and pulmonary and systemic arterial-venous O2 and CO2 differences increase. IR-type decreases, but R-type increases the mitral E/A ratio. PN-type produces the well-described, pseudo-normal mitral inflow pattern. All three types of LVDD reduce right ventricular (RV) and LV EF, but the latter remains normal or near normal. Simulations show reduced EF is partly restored by an accompanying increase in systolic stiffness, a compensatory mechanism that may lead clinicians to miss the presence of HF if they only consider LVEF and other indices of LV function. Simulations using the H-CRS model indicate that changes in RV function might well be diagnostic. This study also highlights the importance of septal mechanics in LVDD.

Conclusion: The model demonstrates that abnormal LV diastolic performance alone can result in decreased LV and RV systolic performance, not previously appreciated, and contribute to the clinical syndrome of HF. Furthermore, alterations of RV diastolic performance are present and may be a hallmark of LV diastolic parameter changes that can be used for better clinical recognition of LV diastolic heart disease.

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Time-Aligned Pressures and Volumes. Time-aligned ventricular and arterial pressures (Panels A1 and A2), chamber volumes (Panels B1 and B2) for the right and left hearts, and septal volume (Panels C1 and C2) in control and different cases of LVDD.
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Figure 7: Time-Aligned Pressures and Volumes. Time-aligned ventricular and arterial pressures (Panels A1 and A2), chamber volumes (Panels B1 and B2) for the right and left hearts, and septal volume (Panels C1 and C2) in control and different cases of LVDD.

Mentions: Previous studies from our group show that septal interaction can profoundly affect right heart function [8]. The septum is modeled as an active pump, governed by an activation function, similar to the ventricular free walls. Only such a description for the septum can produce the correct morphology of ventricular pressure tracings seen experimentally as shown by previous work [8,11]. Septal motion can by analyzed by plotting septal volume (VSPT), shown in Figure 7A3. Focusing on the control curve (black line) at the beginning of the cycle, with early blood flow into the LV there is an upward movement of the VSPT curve which reflects the increased volume of blood in the septum under the influence of the passive left to right pressure gradient across the septum. This initial phase contributes to "priming of the septal pump". As the septum contracts, septal volume decreases indicated by the rapid downward movement of the VSPT curve. Thus, increases in septal volume reflect movement of the septum toward the RV, whereas decreases indicate movement of the septum toward the LV (see volumes model in Figure 1A). The septal contractile downstroke ends with closure of the aortic valve, and septal relaxation begins immediately after aortic valve closure. Hence, there is a strong increase in septal volume during the isovolumic relaxation period. This corresponds to rightward movement of the septum which increases septal volume. When the mitral valve opens, the rapid filling phase begins which is marked by a small positive fluctuation in the general exponential filling curve for VSPT. The cycle of septal activation and relaxation produces biphasic motion, and as a consequence the septum behaves as a third pump along with the RVF and LVF, and contributes to ventricular performance. Septal priming before contraction initiates RV ejection (Figure 7A2), and RV outflow is maximum just as LV outflow is beginning (see downward slopes in VRV and VLV in Figure 7A2 and 7B2). This movement simultaneously aids LV filling (Figure 7B2). The following septal contractile leftward thrust provides support to LV ejection (Figure 7B2). VRV reaches its minimum point and pulmonary arterial flow ends just before the septum reaches its maximum leftward position at the end of aortic flow (Figure 7A1-A3). In late diastole, the septum returns rightward toward its neutral position (Figure 7A3, black dashed line) as the LV fills and the mitral valve closes (Figure 7B1-B3). The tricuspid valve closes shortly thereafter (Figure 7A2).


Modeling left ventricular diastolic dysfunction: classification and key indicators.

Luo C, Ramachandran D, Ware DL, Ma TS, Clark JW - Theor Biol Med Model (2011)

Time-Aligned Pressures and Volumes. Time-aligned ventricular and arterial pressures (Panels A1 and A2), chamber volumes (Panels B1 and B2) for the right and left hearts, and septal volume (Panels C1 and C2) in control and different cases of LVDD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117805&req=5

Figure 7: Time-Aligned Pressures and Volumes. Time-aligned ventricular and arterial pressures (Panels A1 and A2), chamber volumes (Panels B1 and B2) for the right and left hearts, and septal volume (Panels C1 and C2) in control and different cases of LVDD.
Mentions: Previous studies from our group show that septal interaction can profoundly affect right heart function [8]. The septum is modeled as an active pump, governed by an activation function, similar to the ventricular free walls. Only such a description for the septum can produce the correct morphology of ventricular pressure tracings seen experimentally as shown by previous work [8,11]. Septal motion can by analyzed by plotting septal volume (VSPT), shown in Figure 7A3. Focusing on the control curve (black line) at the beginning of the cycle, with early blood flow into the LV there is an upward movement of the VSPT curve which reflects the increased volume of blood in the septum under the influence of the passive left to right pressure gradient across the septum. This initial phase contributes to "priming of the septal pump". As the septum contracts, septal volume decreases indicated by the rapid downward movement of the VSPT curve. Thus, increases in septal volume reflect movement of the septum toward the RV, whereas decreases indicate movement of the septum toward the LV (see volumes model in Figure 1A). The septal contractile downstroke ends with closure of the aortic valve, and septal relaxation begins immediately after aortic valve closure. Hence, there is a strong increase in septal volume during the isovolumic relaxation period. This corresponds to rightward movement of the septum which increases septal volume. When the mitral valve opens, the rapid filling phase begins which is marked by a small positive fluctuation in the general exponential filling curve for VSPT. The cycle of septal activation and relaxation produces biphasic motion, and as a consequence the septum behaves as a third pump along with the RVF and LVF, and contributes to ventricular performance. Septal priming before contraction initiates RV ejection (Figure 7A2), and RV outflow is maximum just as LV outflow is beginning (see downward slopes in VRV and VLV in Figure 7A2 and 7B2). This movement simultaneously aids LV filling (Figure 7B2). The following septal contractile leftward thrust provides support to LV ejection (Figure 7B2). VRV reaches its minimum point and pulmonary arterial flow ends just before the septum reaches its maximum leftward position at the end of aortic flow (Figure 7A1-A3). In late diastole, the septum returns rightward toward its neutral position (Figure 7A3, black dashed line) as the LV fills and the mitral valve closes (Figure 7B1-B3). The tricuspid valve closes shortly thereafter (Figure 7A2).

Bottom Line: The effects of increasing systolic contractility are also considered.IR-type decreases, but R-type increases the mitral E/A ratio.The model demonstrates that abnormal LV diastolic performance alone can result in decreased LV and RV systolic performance, not previously appreciated, and contribute to the clinical syndrome of HF.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept, Electrical and Computer Engineering, Rice University, Houston, TX 77005, USA.

ABSTRACT

Background: Mathematical modeling can be employed to overcome the practical difficulty of isolating the mechanisms responsible for clinical heart failure in the setting of normal left ventricular ejection fraction (HFNEF). In a human cardiovascular respiratory system (H-CRS) model we introduce three cases of left ventricular diastolic dysfunction (LVDD): (1) impaired left ventricular active relaxation (IR-type); (2) increased passive stiffness (restrictive or R-type); and (3) the combination of both (pseudo-normal or PN-type), to produce HFNEF. The effects of increasing systolic contractility are also considered. Model results showing ensuing heart failure and mechanisms involved are reported.

Methods: We employ our previously described H-CRS model with modified pulmonary compliances to better mimic normal pulmonary blood distribution. IR-type is modeled by changing the activation function of the left ventricle (LV), and R-type by increasing diastolic stiffness of the LV wall and septum. A 5th-order Cash-Karp Runge-Kutta numerical integration method solves the model differential equations.

Results: IR-type and R-type decrease LV stroke volume, cardiac output, ejection fraction (EF), and mean systemic arterial pressure. Heart rate, pulmonary pressures, pulmonary volumes, and pulmonary and systemic arterial-venous O2 and CO2 differences increase. IR-type decreases, but R-type increases the mitral E/A ratio. PN-type produces the well-described, pseudo-normal mitral inflow pattern. All three types of LVDD reduce right ventricular (RV) and LV EF, but the latter remains normal or near normal. Simulations show reduced EF is partly restored by an accompanying increase in systolic stiffness, a compensatory mechanism that may lead clinicians to miss the presence of HF if they only consider LVEF and other indices of LV function. Simulations using the H-CRS model indicate that changes in RV function might well be diagnostic. This study also highlights the importance of septal mechanics in LVDD.

Conclusion: The model demonstrates that abnormal LV diastolic performance alone can result in decreased LV and RV systolic performance, not previously appreciated, and contribute to the clinical syndrome of HF. Furthermore, alterations of RV diastolic performance are present and may be a hallmark of LV diastolic parameter changes that can be used for better clinical recognition of LV diastolic heart disease.

Show MeSH
Related in: MedlinePlus