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

Systolic dysfunction is defined as an impairment of the myocardialfunction (regional or global) during the systole.

It commonly leads to areduction in the ventricular ejection fraction. The role of systolicdysfunction in heart failure has acquired profuse attention from both clinicaland 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 numerousmethods have been developed to quantify and assess the cardiac systolicfunction, ranging from non-invasive cardiac imaging sequences likeechocardiography, magnetic resonance imaging (MRI) and computer tomography (CT)to invasive hemodynamic measurements using heart catheterization.

The earlyechocardiographic assessment of the LV function comprised of two-dimensionalmeasurement of the left ventricular ejection fraction (LV-EF) and qualitativeanalysis of regional wall motion abnormalities. Echocardiography is the mostcommonly used method to estimate the LV-EF in a clinical setting. A reductionin LV-EF is associated with a poor prognosis and is acknowledged by theresearch 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 pathomechanismof heart failure has been under-represented in early clinical trials and hasyielded less interest from the research community (Gaasch and Zile,2004; Zile and Brutsaert, 2002a; Zile and Brutsaert, 2002b) in comparison tosystolic dysfunction. Diastolic dysfunction is defined as an impairment inmyocardial relaxation, distensibility or filling, which consequently leads toan increase in the end diastolic left ventricular pressures (LV-EDP). A broad appreciationof cardiac physiology in the diastole and the cardiovascular compensationmechanisms are needed to fully comprehend the pathomechanisms leading to heartfailure symptoms (Amr et al.

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,2016; Yancy et al., 2013; Zile andBrutsaert, 2002b). The clinical identificationof diastolic dysfunction presents many difficulties.

Hemodynamic assessment andmeasurements of intra-cardiac pressures using heart catheterization are the currentgold standard in diagnosing diastolic dysfunction. The echocardiographicassessment, including tissue Doppler imaging and Doppler measurements of thetransmitral flow, is the non-invasive gold-standard in the evaluation ofdiastolic dysfunction (Amr et al.,2016; Yancy et al., 2013).

            The impairment ofcardiac function in patients with DCM cannot be solely attributed to systolicor diastolic dysfunction. A global reduction in the systolic contractility ofthe ventricle would consequently lead to an impairment of myocardialrelaxation, which per definition, affects the diastolic function. Computationalcardiac models with different levels of complexity and functionality could be utilizedto gain a better understanding of these processes. Furthermore, in-silico simulations of cardiacfunction have the potential of identifying new prognostic markers and promiseto improve therapy planning.