The fundamental mechanisms of diastolic dysfunction are impaired relaxation, loss of restoring forces, and increased diastolic stiffness, and as a compensatory mechanism to maintain cardiac output, there is elevation of LA pressure. The latter response involves reflex mediated venoconstriction with translocation of blood towards the central circulation, which is a fast response, and fluid retention in the kidneys as a slower mechanism. In the early phase of diastolic dysfunction, LV filling pressure may be normal at rest and elevated only during physical exercise (Fig. 4).
Typical for normal diastolic function is rapid relaxation and vigorous restoring forces which result in low or even negative minimum LV diastolic pressure, causing high mitral pressure gradient and dominance of early diastolic LV filling. Myocardial relaxation reflects rate of calcium reuptake from the cytosol. Restoring forces reflect LV systolic function and are generated when the ventricle contracts below its unstressed volume, analogous to manual compression of a tennis ball which recoils back to its original round shape when compression is released. When there is normal rapid LV relaxation, restoring forces generate negative minimum diastolic pressures and imply that the LV wall performs work to pull blood into the ventricle, representing filling by suction. There is also an alternative definition of suction, which is LV filling during falling pressure, which does not include negative LV pressure or release of restoring forces. This definition also is useful, as shown in studies of LA filling, as illustrated in Fig. 3.
Relaxation and restoring forces may be evaluated by measuring e′ and untwisting velocity by echocardiography [13,14,15,16], but currently only e′ is used clinically, as there are methodological challenges with measuring untwisting velocity. When invasive pressure is available, the time constant of LV isovolumic pressure fall may be used to quantify LV relaxation , but currently mainly for research purposes (Fig. 5). Relaxation and restoring forces exert their effects simultaneously, and clinically there is no way to measure each component separately.
Experimental data show that the normal LV may generate negative early diastolic pressure which sucks blood into the ventricle. This mechanism is attenuated or lost in heart failure, as demonstrated by Little’s group in chronic dog experiments (Fig. 6) . Presumably, a similar mechanism is operative in normal human hearts and causes filling by suction [19, 20]. The interaction between LV end-systolic volume, restoring forces, and diastolic filling illustrates the tight coupling between systolic and diastolic function. Mitral-to-apical flow propagation velocity by color flow imaging is a parameter of early diastolic function, but is currently not widely used .
Left ventricular diastolic compliance is a lumped parameter and is determined not only by LV myocardial compliance, but also by elastic properties of extraventricular structures (pericardium and lungs) and by right ventricular diastolic pressure. The term LV chamber compliance is often used rather than just LV compliance, with the latter referring to myocardial compliance. Because the LV pressure–volume relationship is curvilinear, chamber compliance is a function of the operative LV diastolic pressure. As an example, elevation of LV diastolic pressure by volume loading, which moves the LV pressure–volume coordinate to a steeper part of the pressure–volume curve, causes reduction in chamber compliance in a ventricle which is entirely normal. Therefore, reduced chamber compliance does not necessarily mean there has been a change in myocardial elastic properties. Figure 5 shows diastolic pressure–volume curves from a group of normal individuals compared with patients with heart failure and preserved EF and reduced EF, respectively.
Different mitral filling patterns are displayed in Fig. 7. The pattern of impaired relaxation (grade I) has low E and tall A. The pattern of pseudonormalized filling (grade II) has flow velocities similar to a normal heart and is identified by reduced e′. The pattern with tall E with short deceleration time (<150 ms), combined with small A and E/A > 2 is named restrictive filling (grade III) and is associated with reduced LV diastolic compliance  (Fig. 8). By definition, grades II and III diastolic dysfunction have elevated LV filling pressure, which can be determined according to the algorithm presented in Fig. 9. The relationship between E deceleration time and degree of diastolic dysfunction is nonlinear; therefore, in mild diastolic dysfunction dominated by impaired relaxation, there is prolongation of E deceleration time because of ongoing relaxation during flow deceleration. Importantly, in young healthy individuals with high mitral E, there is often a deceleration time <150 ms. Therefore, a short deceleration time should not be used as a standalone index of reduced LV compliance. Healthy people, however, do not have a large A
r, which is typical for ventricles with reduced compliance as discussed below.
Reduction in LV chamber compliance is also reflected in attenuation and abbreviation of the transmitral A velocity and is typically combined with accentuation and prolongation of the pulmonary vein A
r [7, 8]. When the atrium contracts against a ventricle with reduced compliance, little blood moves forward across the mitral valve, antegrade mitral flow is interrupted prematurely, and instead blood regurgitates into the more compliant pulmonary veins. When the duration of A
r exceeds the duration of mitral A by >30 ms, it is consistent with elevated LV end-diastolic pressure. The limitations of A duration difference as an index of diastolic compliance include atrial mechanical failure and suboptimal quality of the pulmonary venous flow signal. Furthermore, even in patients with severe diastolic dysfunction, a large A
r may be absent when there is prolonged atrioventricular conduction or tachycardia, so that atrial contraction takes place before diastolic pulmonary venous flow (D) is completed. In these cases, the difference in A duration does not reflect LV filling pressure.
Thus, a short mitral E deceleration time together with a small and abbreviated mitral A and a large A
r of long duration are consistent with reduced LV compliance.