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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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Related in: MedlinePlus

Model Ventricular Function Curves - Septal Stiffness Comparison. Simulated ventricular function curves of normal physiology (control, C), increased LV wall and septal stiffness (R), and increased LV wall but normal septal stiffness (RNSPT). All simulations performed with normal systolic contractility.
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Figure 10: Model Ventricular Function Curves - Septal Stiffness Comparison. Simulated ventricular function curves of normal physiology (control, C), increased LV wall and septal stiffness (R), and increased LV wall but normal septal stiffness (RNSPT). All simulations performed with normal systolic contractility.

Mentions: In the P-V loops of Figure 10A1 and 10B1, the curve labeled R simulates R-type LVDD with elevated levels of stiffness for both the free wall and septum (as in Figure 3). The curve labeled RNSPT represents a second simulation where the septal stiffness is set to normal control levels, all other conditions being the same. Focusing on the LV ejection phase of the P-V loops in Figure 10B1, the simulated progression of septal disease RNSPT → R causes the septum to support free wall pumping to a lesser degree, diminishing the "ramping up" of LV pressure during the ejection phase and reducing stroke volume. Changes in septal stiffness also have a pronounced effect on the P-V loops of the RV (Figure 10A1). The ejection phase is downward in the P-V loop in control. With increased LV wall and then septal stiffness, this slope changes to upward, indicative of the increased afterload imposed on the ejecting RV.


Modeling left ventricular diastolic dysfunction: classification and key indicators.

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

Model Ventricular Function Curves - Septal Stiffness Comparison. Simulated ventricular function curves of normal physiology (control, C), increased LV wall and septal stiffness (R), and increased LV wall but normal septal stiffness (RNSPT). All simulations performed with normal systolic contractility.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: Model Ventricular Function Curves - Septal Stiffness Comparison. Simulated ventricular function curves of normal physiology (control, C), increased LV wall and septal stiffness (R), and increased LV wall but normal septal stiffness (RNSPT). All simulations performed with normal systolic contractility.
Mentions: In the P-V loops of Figure 10A1 and 10B1, the curve labeled R simulates R-type LVDD with elevated levels of stiffness for both the free wall and septum (as in Figure 3). The curve labeled RNSPT represents a second simulation where the septal stiffness is set to normal control levels, all other conditions being the same. Focusing on the LV ejection phase of the P-V loops in Figure 10B1, the simulated progression of septal disease RNSPT → R causes the septum to support free wall pumping to a lesser degree, diminishing the "ramping up" of LV pressure during the ejection phase and reducing stroke volume. Changes in septal stiffness also have a pronounced effect on the P-V loops of the RV (Figure 10A1). The ejection phase is downward in the P-V loop in control. With increased LV wall and then septal stiffness, this slope changes to upward, indicative of the increased afterload imposed on the ejecting RV.

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