Limits...
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.

Show MeSH

Related in: MedlinePlus

Model Waveforms for Right and Left Ventricles in Control Case. Model-generated pressure, volume and flow waveforms for the normal patient (control case). PFR = peak filling rate (slope of drawn line); RFF = rapid filling fraction; AFF = atrial filling fraction; IVRT = isovolumic relaxation time; DT = E-wave deceleration time; (P)AO/C = (pulmonary) aortic valve opens/closes; MVO/C = mitral valve opens/closes; TVO/C = tricuspid valve opens/closes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3117805&req=5

Figure 2: Model Waveforms for Right and Left Ventricles in Control Case. Model-generated pressure, volume and flow waveforms for the normal patient (control case). PFR = peak filling rate (slope of drawn line); RFF = rapid filling fraction; AFF = atrial filling fraction; IVRT = isovolumic relaxation time; DT = E-wave deceleration time; (P)AO/C = (pulmonary) aortic valve opens/closes; MVO/C = mitral valve opens/closes; TVO/C = tricuspid valve opens/closes.

Mentions: Model-generated tracings of normal cardiac function are shown in Figure 2 for the right (Panels A1-A4) and left ventricles (Panels B1-B4). These are considered control waveforms for comparison with simulations of diastolic dysfunction. Of particular note are the tricuspid (QTC) and mitral (QM) flow waveforms shown in Figure 2A3 and 2B3, respectively. These waveforms have an early (E wave) and a late (A wave) component during diastolic ventricular filling. Normally, the E/A ratio is 1 - 1.5 and the trans-mitral deceleration time (DT; Figure 2B3) during rapid filling (E wave) is 170 - 230 ms [7]. The central venous (QVC) and distal pulmonary venous (QPV) flow waveforms are shown in Figure 2A4 and 2B4, respectively. These waveforms consist of systolic (S), diastolic (D) and atrial reversal (AR) flow components. The normal systolic pulmonary venous S wave is split into early and late components (S1 and S2; Figure 2B4). Table 2 lists the indices for both right and left ventricular performance and the mean values of systemic circulatory variables, blood gas tensions, and A-V gas differences in the brain and extra-cranial tissues. Figure 3 (solid black line labeled C for control) depicts the normal instantaneous RV and LV pressure-volume relationships. The other loops and curves of the three modeled LVDD types are discussed below.


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 Waveforms for Right and Left Ventricles in Control Case. Model-generated pressure, volume and flow waveforms for the normal patient (control case). PFR = peak filling rate (slope of drawn line); RFF = rapid filling fraction; AFF = atrial filling fraction; IVRT = isovolumic relaxation time; DT = E-wave deceleration time; (P)AO/C = (pulmonary) aortic valve opens/closes; MVO/C = mitral valve opens/closes; TVO/C = tricuspid valve opens/closes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Model Waveforms for Right and Left Ventricles in Control Case. Model-generated pressure, volume and flow waveforms for the normal patient (control case). PFR = peak filling rate (slope of drawn line); RFF = rapid filling fraction; AFF = atrial filling fraction; IVRT = isovolumic relaxation time; DT = E-wave deceleration time; (P)AO/C = (pulmonary) aortic valve opens/closes; MVO/C = mitral valve opens/closes; TVO/C = tricuspid valve opens/closes.
Mentions: Model-generated tracings of normal cardiac function are shown in Figure 2 for the right (Panels A1-A4) and left ventricles (Panels B1-B4). These are considered control waveforms for comparison with simulations of diastolic dysfunction. Of particular note are the tricuspid (QTC) and mitral (QM) flow waveforms shown in Figure 2A3 and 2B3, respectively. These waveforms have an early (E wave) and a late (A wave) component during diastolic ventricular filling. Normally, the E/A ratio is 1 - 1.5 and the trans-mitral deceleration time (DT; Figure 2B3) during rapid filling (E wave) is 170 - 230 ms [7]. The central venous (QVC) and distal pulmonary venous (QPV) flow waveforms are shown in Figure 2A4 and 2B4, respectively. These waveforms consist of systolic (S), diastolic (D) and atrial reversal (AR) flow components. The normal systolic pulmonary venous S wave is split into early and late components (S1 and S2; Figure 2B4). Table 2 lists the indices for both right and left ventricular performance and the mean values of systemic circulatory variables, blood gas tensions, and A-V gas differences in the brain and extra-cranial tissues. Figure 3 (solid black line labeled C for control) depicts the normal instantaneous RV and LV pressure-volume relationships. The other loops and curves of the three modeled LVDD types are discussed below.

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