Abstract
Correlation of the thickness of the left ventricular posterior wall (LVPWd) with various parameters, including age, gender, weight and height, was investigated in this study using regression models. Multicenter derived database comprised over 4,000 healthy individuals. The developed models were further utilized in the in vitro–in vivo (IVIV) translation of the drug cardiac safety data with use of the mathematical model of human cardiomyocytes operating at the virtual healthy population level. LVPWd was assumed to be equivalent to the length of one-dimensional string of virtual cardiomyocyte cells which was presented, as other physiological factors, to be a parameter influencing the simulated pseudo-ECG (pseudoelectrocardiogram), QTcF and ∆QTcF, both native and modified by exemplar drug (disopyramide) after I Kr current disruption. Simulation results support positive correlation between the LVPWd and QTcF/∆QTc. Developed models allow more detailed description of the virtual population and thus inter-individual variability influence on the drug cardiac safety.Electronic supplementary materialThe online version of this article (doi:10.1007/s12265-014-9558-4) contains supplementary material, which is available to authorized users.
Highlights
Echocardiography has become one of the dominant cardiac imaging techniques as it has good temporal and spatial resolution, and it is widely available given its low costs compared to other imaging modalities
There are many parameters that are routinely assessed by echocardiography, e.g., wall thicknesses, ventricular dimensions, volumes, masses and ventricular function [3, 4]
Their study group consisted of 136 healthy subjects (78 men and 58 women, aged 20–97 years), but the sex of the subjects was not included in their regression models
Summary
Echocardiography has become one of the dominant cardiac imaging techniques as it has good temporal and spatial resolution, and it is widely available given its low costs compared to other imaging modalities. There has been only a handful of studies investigating the effect of different demographic and physiological parameters on the left ventricular posterior wall thickness (LVPWd) in healthy adults. The fact that they were written in 1990s can potentially leads to concerns regarding their consistency with the best current clinical practice, both in terms of clinical guidelines and accuracy of measurement equipment and measurement technique applied. There were LVPWd models developed for pediatric populations, but since they are out of the scope of the current study, we will only mention the Carceller and colleagues study [8] They developed a model correlating BSA with the LVPWd, based on a group of 69 healthy individuals aged 10–20 years
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