As already discussed in Part 3, we can be free from the criticisms if we call diastolic function as ‘filling function’ Moreover, helpful in understanding the evaluation of diastolic function. Diastolic function can be represented by the filling function of this roller pump model. Tube in this roller pump must expand rapidly and fully immediately after the squeeze by the roller, therefore, can quickly and adequately suck the fluid into the pump. Otherwise, if tube is not adequately filled by the fluid, pumping function cannot be maintained even if roller can completely squeeze the tube and how fast roller spins. Tube function of this roller pump is the ‘filling function’, that is, the ‘diastolic function’. There are two types of abnormalities in the tube function. 1st is the sticky tube and 2nd is stiff tube. In sticky tube, tube expands slowly, does not expands well, at the initial expansion but does not need high pressure to expands further once expanded. In stiff tube, tube expands rather rapidly at the initial expansion but needs high pressure if the tube to be expanded further. These situations are very similar to the abnormal relaxation and the increased passive stiffness in the heart. If we take a look at the LV filling during diastole, during early diastole, pulling action of LV suction is more important than role of LA pressure pushing the blood into LV. However, during late diastole, LV should be compliant enough to accommodate adequate amount of blood at the given pushing action of LA contraction. Therefore abnormal relaxation predominantly affects early phase of diastole, the period when the diastolic suction is important. Increased passive stiffness affects mid to late phase of diastole. After the corner stone work by Dr. Kitabatake in the evaluation of diastolic function by using PW Doppler mitral inflow pattern, mitral inflow has been most fundamental parameter in the evaluation of diastolic – LV filling – function. As the mitral inflow is determined by the pressure gradient between LA and LV diastolic pressure, in the case of relaxation abnormality, increase in LV volume is slower than in the case of normal relaxation. Accordingly, LV pressure decay during early diastole is slower than the normal. Not in the presence of change in LA pressure, maximum difference in pressure gradient between LA and LV diastolic pressure is reduced, rate of decrease in the pressure gradient between the two is slowed, which results in decreased E velocity and prolongation of the deceleration time. Decrease in early diastolic filling is compensated by the increase in late diastolic filling, that is, increase in A velocity resulting in reversed E/A ratio. Not to mention, isovolumic relaxation period (IVRT), time interval between aortic valve closure to mitral valve opening, increases, as you see in the figure.. Normal mitral inflow pattern on the left changes into relaxation abnormality pattern on the right. One of the limitations of mitral inflow patterns is…, mitral inflow does not represent the myocardial relaxation itself, but represents only the pressure gradient between LA and LV diastolic pressures. Without change in LV relaxation, when the LA pressure rises, E velocity rises again with shortening of deceleration time, mimicking normal mitral inflow pattern, called ‘pseudonormal filling pattern’. If there is a further rise in LA pressure, further elevation of E velocity and shortening of deceleration time follows, associated with E/A ratio of>2, which is called ‘ restrictive physiology’ Restrictive physiology, which is regarded as the most advanced stage of diastolic dysfunction, can be sub-classified into reversible and irreversible restrictive filling patterns. Reversible restrictive filling pattern is defined as the restrictive filling pattern that changes into relaxation abnormality pattern when the loading condition is reduced. Irreversible restrictive filling pattern is defined as the persistent restrictive filling pattern even when the loading condition is reduced. Different prognosis was reported between the two filling patterns. Mayo clinic proposed 4 grades in diastolic dysfunction. This grading is widely used in our daily practice as it is convenient to suggest the status of the patient in a simple way. With tissue Doppler imaging, we can get the wall motion velocity using Doppler technology. If we put the sample volume on the mitral annulus, we can get the ‘mitral annulus velocity’. In the mitral annulus velocity profile, we can notice 2 velocities toward the LA side, which imply rate of LV volume increase in long axis. We call these velocities as E’ and A’ velocities, respectively. E’ velocity in the mitral annulus velocity, as we mentioned earlier, implies rate of increase in LV volume in long axis after mitral valve opening. Rate of volume increase in long axis, without distortion in LV geometry, is likely to represent rate of global increase in LV volume. Therefore, E’ velocity can represent LV relaxation during early diastole, immediately after mitral valve opening. As the ‘timing’ is after the mitral valve opening, theoretically, LA pressure can affect the relaxation rate of LV. But, probably less affected compared to the mitral inflow, which represent pressure gradient between LA and LV diastolic pressures. In another word, mitral annulus velocity is less dependent on the loading condition compared to the mitral inflow. As you see here, mitral inflow shows parabolic nature of changes in E velocity with the changes in loading condition, as this parameter is dependent on the loading conditon, E’ velocity in the mitral annulus velocity shows sequential changes from normal to restrictive physiology, as this velocity is relatively preload independent. Therefore, if we consider mitral inflow and mitral annulus velocity together in the evaluation of diastolic function, we can easily tell the types of diastolic dysfunction. Abnormality in relaxation can be evaluated as we discussed so far. Evaluation of the abnormality in ‘passive stiffness’ is very much limited. It might be safe to say that prediction of the ‘ likelihood of having far abnormal passive stiffness’ is possible with our current methodology. For the evaluation of passive stiffness, we can apply the method of assessing passive stiffness in an elastic material. Passive stiffness can be evaluated in the relation between stress (the force imposed on) and the strain (degree of deformation). In this equation, ‘stress’ can be replaced by the ‘LV pressure change’ and ‘strain’ by the ‘LV volume change’. If we obtain pressure-volume loop of LV, stress-strain relationship ‘at end-diastole’, phenomenon occurring when active relaxation is completed, can provide us the idea of the physical property of the myocardium – ‘passive stiffness’. Method of obtaining LV volume data in real time is not practically easy in human. Moreover, we should alter the loading condition not in just 2 times but multiple times as the relationship is not linear but curvelinear. Therefore, this method is not clinically feasible yet, is used only in the laboratory setting. Critical limitation in the assessment of ‘ passive stiffness’ is… We will pursue to apply the method(s) we have discussed if the myocardium is an elastic material, however, myocardium has a viscous property, as well as an elastic property – ‘viscoelastic’, therefore, quantitative assessment of the passive stiffness of the myocardium lies far beyond our ability to measure. In patient who cannot extend his knee fully, it is important to know the cause (etiology) of his disability, whether due to the joint problem or due to the muscle problem. It is important to know the ’cause’ in the therapeutic aspect. But in the evaluation of the response to treatment, regardless of the cause, ‘range of motion’ is out utmost interest. Likewise, it is important to know the type of diastolic dysfunction in a given patient. But in our practice, information about the filling pressure is sometimes more valuable than the information about the type of diastolic dysfunction. We can have qualitative nature of LV filling pressure from the mitral inflow patterns. But from the mitral inflow and mitral annulus velocities, LV filling pressure can be estimated more quantitatively. E velocity in the mitral inflow is determined by the LV filling pressure and the property of myocardial relaxation. Therefore, information about the filling pressure of LV can be obtained by correcting the mitral inflow with the parameter representing myocardial relaxation. E’ velocity in the mitral annulus velocity, as this velocity is relatively preload independent, can be used as a parameter representing myocardial relaxation. Therefore, E velocity over E’ velocity can represent LV filling pressure. In a number of studies, E/E’ ratio showed good correlations with LV filling pressure. Although there is a gray zone, ‘normal filling pressure’ is expected when this ratio is under 8 and ‘high filling pressure’ when this ratio is over 15. In the beginning of Part 3, we have discussed about the issue of including constriction in the diastolic heart failure. If we define the diastolic heart failure as ‘ heart failure with abnormal filling function’, constriction can be included in the diastolic heart failure. Diagnostic criteria for constrictive pericarditis in the past concentrated only on the LV filling pattern. These ventricular filling patterns are also seen in restrictive cardiomyopathy. Therefore, it is quite a natural consequence that differentiation between constrictive pericarditis and restrictive cardiomyopathy is a tough task even to the experts. Two distinct features of constrictive pericarditis are 1) exaggeration of ventricular interdependence because two ventricles are sharing the fixed space, 2) dissociation between intracavitary and intrathoracic pressures because of the thick pericardium. Mitral annulus velocity is useful in constrictive pericarditis. In contrast to other pathologic conditions, E’ velocity is increased, in contrast to the decreased E’ in most of the diseases, in constrictive pericarditis. Left panel is the mitral annulus velocity in constrictive pericarditis. In the right panel, annulus velocity decreased after pericardiectomy when the constrictive physiology is relieved. Therefore, differentiation between constrictive pericarditis and restrictive cardiomyopathy is quite easy with mitral annulus velocity. Restrictive cardiomyopathy, which is a myocardial disease, shows decreased E’ velocity. In sharp contrast to the constrictive pericarditis, in which E’ velocity is exaggerated. Thank you for your attention.