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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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Influence of Respiratory Variation. Transvalvular flow variation (QTC shown in Panels A1-A4 and QM shown in Panels B1-B4) during a cycle of respiration (expiration (Exp.) and inspiration (Insp.) are marked). The red lines trace the respiratory variation. Pulmonary vasculature volume is shown in Panels C1-C4. Pulmonary blood volume increases with LVDD, with IR-type LVDD having the lowest increase and PN-type LVDD having the highest increase.
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Figure 13: Influence of Respiratory Variation. Transvalvular flow variation (QTC shown in Panels A1-A4 and QM shown in Panels B1-B4) during a cycle of respiration (expiration (Exp.) and inspiration (Insp.) are marked). The red lines trace the respiratory variation. Pulmonary vasculature volume is shown in Panels C1-C4. Pulmonary blood volume increases with LVDD, with IR-type LVDD having the lowest increase and PN-type LVDD having the highest increase.

Mentions: Pleural pressure affects cardiac flows, commonly observed as variation in transvalvular flows coincident with respiration. In a healthy individual, inspiration causes an increase in systemic inflow, increasing QTC in comparison to QTC during expiration. As a result, this variation in systemic inflow is carried across through the pulmonary circulation to the left heart inflow, whereby 2-3 heartbeats later, (roughly coincident with expiration) QM is at a maximum, and during inspiration QM is at its minimum [20]. The model respiratory waveform used in this study is roughly sinusoidal, varying from -2 to -6 mmHg over a 7-second period, and has been used in previous studies [7,8,11]. Our simulations show that the percent respiratory variation (percent deviation from maximum flow) in control QTC is 24.2% and 5.5% in QM (Table 5 and Figure 13A1 and 13B1). In LVDD, respiratory variation in QTC becomes much more pronounced, with values of 36.9%, 48.1% and 70.1% for the IR, R and PN cases, respectively (Table 5 and Figure 13A2-A4). Respiratory influence on mitral flow QM is weak, but can be seen in the control case (Figure 13B1). In LVDD, there is a progressive reduction in percent respiratory variation in QM in the direction IR → R → PN LVDD (Table 5 and Figure 13B2-B4). Concurrently, pulmonary blood volume increases in the same direction of IR → R → PN LVDD (Figure 13C2-C4), acting as a buffer against left heart respiratory variation. This increase in pulmonary blood volume is accompanied by increased afterload on the RV and hence RV pressure increases (Figure 3A). The buffering effect of the pulmonary blood volume seemingly decouples the respiratory variation so that it mainly affects the right heart as RV systolic pressures increase and diastolic pressures decrease, becoming even more influenced by PPL and less influenced by the septum. Moreover, the mean position of the septum is displaced rightward in IR-type, and leftward in R-type and PN-type LVDD (Figure 7A3), with attendant loss of pumping efficiency in all LVDD cases relative to control.


Modeling left ventricular diastolic dysfunction: classification and key indicators.

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

Influence of Respiratory Variation. Transvalvular flow variation (QTC shown in Panels A1-A4 and QM shown in Panels B1-B4) during a cycle of respiration (expiration (Exp.) and inspiration (Insp.) are marked). The red lines trace the respiratory variation. Pulmonary vasculature volume is shown in Panels C1-C4. Pulmonary blood volume increases with LVDD, with IR-type LVDD having the lowest increase and PN-type LVDD having the highest increase.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 13: Influence of Respiratory Variation. Transvalvular flow variation (QTC shown in Panels A1-A4 and QM shown in Panels B1-B4) during a cycle of respiration (expiration (Exp.) and inspiration (Insp.) are marked). The red lines trace the respiratory variation. Pulmonary vasculature volume is shown in Panels C1-C4. Pulmonary blood volume increases with LVDD, with IR-type LVDD having the lowest increase and PN-type LVDD having the highest increase.
Mentions: Pleural pressure affects cardiac flows, commonly observed as variation in transvalvular flows coincident with respiration. In a healthy individual, inspiration causes an increase in systemic inflow, increasing QTC in comparison to QTC during expiration. As a result, this variation in systemic inflow is carried across through the pulmonary circulation to the left heart inflow, whereby 2-3 heartbeats later, (roughly coincident with expiration) QM is at a maximum, and during inspiration QM is at its minimum [20]. The model respiratory waveform used in this study is roughly sinusoidal, varying from -2 to -6 mmHg over a 7-second period, and has been used in previous studies [7,8,11]. Our simulations show that the percent respiratory variation (percent deviation from maximum flow) in control QTC is 24.2% and 5.5% in QM (Table 5 and Figure 13A1 and 13B1). In LVDD, respiratory variation in QTC becomes much more pronounced, with values of 36.9%, 48.1% and 70.1% for the IR, R and PN cases, respectively (Table 5 and Figure 13A2-A4). Respiratory influence on mitral flow QM is weak, but can be seen in the control case (Figure 13B1). In LVDD, there is a progressive reduction in percent respiratory variation in QM in the direction IR → R → PN LVDD (Table 5 and Figure 13B2-B4). Concurrently, pulmonary blood volume increases in the same direction of IR → R → PN LVDD (Figure 13C2-C4), acting as a buffer against left heart respiratory variation. This increase in pulmonary blood volume is accompanied by increased afterload on the RV and hence RV pressure increases (Figure 3A). The buffering effect of the pulmonary blood volume seemingly decouples the respiratory variation so that it mainly affects the right heart as RV systolic pressures increase and diastolic pressures decrease, becoming even more influenced by PPL and less influenced by the septum. Moreover, the mean position of the septum is displaced rightward in IR-type, and leftward in R-type and PN-type LVDD (Figure 7A3), with attendant loss of pumping efficiency in all LVDD cases relative to control.

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