Modeling left ventricular diastolic dysfunction: classification and key indicators

Abstract

BackgroundMathematical 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.MethodsWe 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.ResultsIR-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.ConclusionThe 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.

Sustained therapeutic hypercapnia attenuates pulmonary arterial Rho-kinase activity and ameliorates chronic hypoxic pulmonary hypertension in juvenile rats

“…A limitation of the present study is that we were unable to quantify LV diastolic function, which may also be adversely affected by hypercapnic acidosis (70), due to an inability to reliably acquire the required four-and five-chamber views to perform transmitral Doppler, described in mature murine models (56,72). Although our finding that PVR was significantly improved and that LV systolic function was not adversely affected (or was perhaps increased) by chronic hypercapnia suggests a decreased likelihood of diastolic dysfunction (38), this issue warrants future study employing catheter-based measurement.…”

Prognostic value of echocardiography and ECG in heart failure with preserved ejection fraction

“…Nevertheless, not solely pulmonary hypertension causes the RV dysfunction. Septal dysfunction related to the LV diastolic dysfunction leads to a decrease of the septal role in the RV ejection and thus causes a systolic mechanical dyssynchrony of the RV (24). There is only limited evidence about the prognostic importance of RV systolic dysfunction in HFPEF (21,25,26).…”

“…There is only limited evidence about the prognostic importance of RV systolic dysfunction in HFPEF (21,25,26). Irrespective of the mechanism of the RV dysfunction and the examination technique, the RV systolic dysfunction is an independent predictor of a poor prognosis in patients with HF in general (13,(23)(24)(25). We observed in our study that the preserved RV systolic function was an independent predictor of a better survival in HFPEF.…”

Management of Pulmonary Hypertension due to Heart Failure with Preserved Ejection Fraction

“…This results in increased load for the right ventricle (RV) endocardium. Many patients with LV diastolic dysfunction also have septal dysfunction, which can worsen RV function [13]. Even though the LVEF is normal in HFpEF, LV contractility may be impaired [14].…”