Systolic al., 1997; Likoff et al., 1987; Ponikowski

Systolic dysfunction is defined as an impairment of the myocardial
function (regional or global) during the systole. It commonly leads to a
reduction in the ventricular ejection fraction. The role of systolic
dysfunction in heart failure has acquired profuse attention from both clinical
and experimental research over the last decades (Bart et al.,
1997; Cohn et al., 1993; Hallstrom et al., 1995; Juillière et al., 1997; Likoff et al., 1987; Ponikowski et al., 2016) and numerous
methods have been developed to quantify and assess the cardiac systolic
function, ranging from non-invasive cardiac imaging sequences like
echocardiography, magnetic resonance imaging (MRI) and computer tomography (CT)
to invasive hemodynamic measurements using heart catheterization. The early
echocardiographic assessment of the LV function comprised of two-dimensional
measurement of the left ventricular ejection fraction (LV-EF) and qualitative
analysis of regional wall motion abnormalities. Echocardiography is the most
commonly used method to estimate the LV-EF in a clinical setting. A reduction
in LV-EF is associated with a poor prognosis and is acknowledged by the
research community as a predictor of survival (Juilliere et al., 1997; Juilliere et al., 1988; Keogh et al., 1988; Komajda et al.,
1990; Likoff et al., 1987).

The role of diastolic dysfunction in the pathomechanism
of heart failure has been under-represented in early clinical trials and has
yielded less interest from the research community (Gaasch and Zile,
2004; Zile and Brutsaert, 2002a; Zile and Brutsaert, 2002b) in comparison to
systolic dysfunction. Diastolic dysfunction is defined as an impairment in
myocardial relaxation, distensibility or filling, which consequently leads to
an increase in the end diastolic left ventricular pressures (LV-EDP). A broad appreciation
of cardiac physiology in the diastole and the cardiovascular compensation
mechanisms are needed to fully comprehend the pathomechanisms leading to heart
failure symptoms (Amr et al.,
2016; Yancy et al., 2013; Zile and
Brutsaert, 2002b). The clinical identification
of diastolic dysfunction presents many difficulties. Hemodynamic assessment and
measurements of intra-cardiac pressures using heart catheterization are the current
gold standard in diagnosing diastolic dysfunction. The echocardiographic
assessment, including tissue Doppler imaging and Doppler measurements of the
transmitral flow, is the non-invasive gold-standard in the evaluation of
diastolic dysfunction (Amr et al.,
2016; Yancy et al., 2013).

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            The impairment of
cardiac function in patients with DCM cannot be solely attributed to systolic
or diastolic dysfunction. A global reduction in the systolic contractility of
the ventricle would consequently lead to an impairment of myocardial
relaxation, which per definition, affects the diastolic function. Computational
cardiac models with different levels of complexity and functionality could be utilized
to gain a better understanding of these processes. Furthermore, in-silico simulations of cardiac
function have the potential of identifying new prognostic markers and promise
to improve therapy planning.