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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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Ventricular Free Wall and Septal Elastance. Plots of RV free wall (Panel A), LV free wall (Panel B), and septal (Panel C) elastance. Open circles indicate outlet (pulmonic and aortic) valve opening, closed circles indicate outlet valve closure. Septal elastance bears a sharp peak coincident with RVF and LVF maximum elastance in control (black line). With IR-type (red line), LVF and septal elastance depict abnormal relaxation, and the peaks widen. With R-type (blue line), septal elastance peak is delayed, occurring after free wall elastance peaks, delaying aortic valve closure. With PN-type (green line), plots show signs of both effects with abnormal LVF and septal elastance downstroke, and delayed and widened septal elastance peak. In all LVDD cases, pulmonic valve opening is delayed. See text for details.
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Figure 8: Ventricular Free Wall and Septal Elastance. Plots of RV free wall (Panel A), LV free wall (Panel B), and septal (Panel C) elastance. Open circles indicate outlet (pulmonic and aortic) valve opening, closed circles indicate outlet valve closure. Septal elastance bears a sharp peak coincident with RVF and LVF maximum elastance in control (black line). With IR-type (red line), LVF and septal elastance depict abnormal relaxation, and the peaks widen. With R-type (blue line), septal elastance peak is delayed, occurring after free wall elastance peaks, delaying aortic valve closure. With PN-type (green line), plots show signs of both effects with abnormal LVF and septal elastance downstroke, and delayed and widened septal elastance peak. In all LVDD cases, pulmonic valve opening is delayed. See text for details.

Mentions: Elastance plots provide information about the timing and level of contractility of free walls and septum. Figure 8A-C depicts RVF, LVF, and septal elastance (mmHg/ml) (Eqn. 9). Open circles indicate opening of outlet valves, while solid circles indicate their closure. In the control case (black line), peak elastance occurs simultaneously for all three walls. The aortic valve closes at this peak and the septum, at its maximum leftward position (Figure 7B3) then snaps toward the right showing a sharp drop in septal elastance (Figure 8C) and the pulmonic valve remains open for this final phase of RV ejection (Figure 8A). By comparing the RV and LV ejection periods with the point of occurrence of septal contraction, one can gain a sense of the contribution the septum has to the ejection processes. Specifically, peak elastance coinciding for the LVF and septum (Figure 8B-C) at the point when the septum is leftward in position (Figure 7B3) indicates that its role in LV ejection is maximized as both contract at the same time for efficient ejection. Similarly, RV systole ends only as the septum nears full relaxation (Figure 8A and 8C) indicating septal activity is involved strongly in the RV ejection process.


Modeling left ventricular diastolic dysfunction: classification and key indicators.

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

Ventricular Free Wall and Septal Elastance. Plots of RV free wall (Panel A), LV free wall (Panel B), and septal (Panel C) elastance. Open circles indicate outlet (pulmonic and aortic) valve opening, closed circles indicate outlet valve closure. Septal elastance bears a sharp peak coincident with RVF and LVF maximum elastance in control (black line). With IR-type (red line), LVF and septal elastance depict abnormal relaxation, and the peaks widen. With R-type (blue line), septal elastance peak is delayed, occurring after free wall elastance peaks, delaying aortic valve closure. With PN-type (green line), plots show signs of both effects with abnormal LVF and septal elastance downstroke, and delayed and widened septal elastance peak. In all LVDD cases, pulmonic valve opening is delayed. See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: Ventricular Free Wall and Septal Elastance. Plots of RV free wall (Panel A), LV free wall (Panel B), and septal (Panel C) elastance. Open circles indicate outlet (pulmonic and aortic) valve opening, closed circles indicate outlet valve closure. Septal elastance bears a sharp peak coincident with RVF and LVF maximum elastance in control (black line). With IR-type (red line), LVF and septal elastance depict abnormal relaxation, and the peaks widen. With R-type (blue line), septal elastance peak is delayed, occurring after free wall elastance peaks, delaying aortic valve closure. With PN-type (green line), plots show signs of both effects with abnormal LVF and septal elastance downstroke, and delayed and widened septal elastance peak. In all LVDD cases, pulmonic valve opening is delayed. See text for details.
Mentions: Elastance plots provide information about the timing and level of contractility of free walls and septum. Figure 8A-C depicts RVF, LVF, and septal elastance (mmHg/ml) (Eqn. 9). Open circles indicate opening of outlet valves, while solid circles indicate their closure. In the control case (black line), peak elastance occurs simultaneously for all three walls. The aortic valve closes at this peak and the septum, at its maximum leftward position (Figure 7B3) then snaps toward the right showing a sharp drop in septal elastance (Figure 8C) and the pulmonic valve remains open for this final phase of RV ejection (Figure 8A). By comparing the RV and LV ejection periods with the point of occurrence of septal contraction, one can gain a sense of the contribution the septum has to the ejection processes. Specifically, peak elastance coinciding for the LVF and septum (Figure 8B-C) at the point when the septum is leftward in position (Figure 7B3) indicates that its role in LV ejection is maximized as both contract at the same time for efficient ejection. Similarly, RV systole ends only as the septum nears full relaxation (Figure 8A and 8C) indicating septal activity is involved strongly in the RV ejection process.

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