Det medisinske fakultet

Global systolic functional imaging

by 

Asbj°rn St°ylen, Professor, Dr. med.

Department of Circulation and Medical Imaging,
Faculty of Medicine,
NTNU Norwegian University of Science and Technology

The page is part of the website on Strain rate imaging
Contact address: asbjorn.stoylen@ntnu.no


This section updated:   November 2016  

There is more to global function than meets the eye by imaging alone. Iceberg (7/8ths below), Illusissat Icefjord.

This section:

Relating the various systolic measurements to each other and to timing in systole, based on the newest findings of tissue Doppler. An understanding of the concepts of myocardial load and work as given in the section on what strain and strain rate actually measure is an advantage.

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References for all sections





Displacement and velocity

Strain and strain rate

Top, mitral annular displacement curve, being the curve showing the longitudinal shortening of the left ventricle. Below, the tissue velocity curve, which is the temporal derivative of the displacement curve. Comparing to the volume/flow curve, it is evident that there is more complex motions, especially n elation to the isovolumic phases, than is evident from the mere volume diagram to the left. Top, strain curve from mid septum, showing the deformation, below the strain rate (temporal derivative). The curves seem to be very similar to inverted motion and velocity curves, however, deformation will show more regional detail as discussed here. Remark also how the strain curve is similar to the volume curve, showing the same pattern, while the strain rate (temporal derivative of strain) is similar to the flow curve (temporal derivative of volume).



It has been established that the longitudinal shortening of the left ventricle, and thus the longitudinal measures is closest related to the stroke volume and EF, i.e. to the total left ventricular volume change (13, 30 - 35, 56, 59, 60, 64 - 67, 116). Thus, the longitudinal strain is the most important measure, and it is also closely related to the wall thickening and thus internal shortening as discussed here.


 
It is obvious that the LV shortening and the ejection are interrelated. In fact, the LV systolic shortening * the circumferential area should be aproximately equal to the stroke volume.


Stroke volume by Doppler flow velocity integral (VTI) and LVOT diameter. The diameter gives the area, and the velocity time integral gives the distance that an object travels if it follows that velocity curve (v =ds/dt, means that s =  v dt. Multiplied with each other, the area and VTI gives the volume of a cylinder, equal to the stroke volume.
Relation of stroke volume and LV shortening. The volume reduction is LV shortening * LV area at the mitral plane. As area is far higher, the distance is far smaller than the VTI.




The apex beat



The apex beat is well known as a clinical event. The apex is pressed forwards and collides with the chest wall during systole, and marks the location of the cardiac apex on clinical examination.


The apex beat, shown here in a normal apexcardiogram demonstrating that the beat is a systolic event. (Image modified from Hurst: The Heart). AS can be seen, in this case the impiulse wave starts before the 1st heart sound, i.e. before MVC and the start of IVC.
The collision. Musk oxen, Gr°nnedal, Greenland


The apex beat has been characterised by apexcardiography, placing a pressure transducer above the apex, and recording the pressure trace, which then will be a function of the movement of the chest wall. The contraction, however, results in ventricular shortening. Unbalanced, this should logically tend to pull the apex away from the chest wall, being kept in place either by tethering or suction. In both cases this would result in an inverted apex curve.  This is discussed above. Thus, it seems that the main force responsible for pressing the apex toward the chest wall is the recoil from ejection.



The systolic motion of the apex towards the chest wall, even displacing the tissue overlying the apex is visible in this normal echo.
....and can be visualised by the reconstructed M-mode from the same loop. The shape of the curve resembles the apexcardiogram above.


Using tissue Doppler, the initial velocity of the apex towards the chest wall, and the end systolic velocity away from the chest wall are both evident. Forward velocities can be seen to start about at the peak of QRS.
...and the integrated displacement curve shows the same shape as the M-mode above.

However, timing makes the situation more complex. As the anterior apical motion starts before ejection, the recoil mechanism cannot be the full explanation.

The apical motion starts at the same time as the pre ejection spike. At this point, however, there is no ejection, and hence no recoil (unless there is mitral regurgitation, of course). And midwall activation, would tend to pull the apex the other way. Thus, the initial apical motion must be due to some external impulse, probably the impact of the late filling wave from atrial contraction.




Doppler LVOT flow from the subject above. The ejection starts later than the QRS, and thus later than the start of apex beat.   Doppler mitral flow. The apex motion starts close to the end of the A-wave.
Reconstructed colour M-mode from the same person. The inflow during atrial systole can be seen to propagate all the way to the apex, and may be assumed to deliver an impact to the apical myocardium.

Thus it seems that the initial impetus for the apical anterior motion may be atrial filling. Thus, the effect may vary according to the atrial part of the total filling volume, the PQ-time, and factors affecting the flow propagation of the A-wave. However, as the atrial impetus is an event of short duration, the recoil of ejection may still be the main force that presses the apex towards the chest wall as seen below:



Combined image from another patient. In this patient apical motion starts before the QRS, and stops abruptly when the apex is pressed into the chest wall as far as it can go. The apex then stays pressed to the chest wall during the whole of the ejection phase.






Resolving the motion, we see that the anterior motion in this case starts even before the start of QRS (A). (The motion seen in the displacement curve starts below zero because the tracking is set at zero by the ECG marker). Peak forward velocity (B1) is just after the QRS, while the motion stops in systole (B2), but the apex remains in the anterior position. At end systole (by T-wave in ECG), there is the start of backward motion (C), and the apex returns to the diastolic position at D.
Comparing the apex tissue velocity with LVOT flow (aligned by ECG), both start and peak apical velocity occurs before start ejection, but continues into ejection. In this case, even a second peak may be seen starting at start ejection, indicating a second impetus from ejection recoil.
And for illustration the relation between apical displacement and ejection. Apical displacement starts before ejection, and then continues into ejection, and maximal apical displacement is close to peak ejection velocity. The apex remains pressed to the chest wall during most of ejection, until the flow velocity is so low as to not generate sufficient recoil pressure, while the full return to diastolic position is somewhat later.

The pre ejection spike in the base and midwall,  is active, the mechanics ot the pre ejection spike are discussed here.

But this means that while there is initial pre ejection contraction in the base and midwall, resulting the MVC as discussed above, this would tend to pull the apex away from the chest wall as there is no recoil force at that point. However, there is an impact from the blood coming nto the ventricle, which pushes the apex towards the chest wall already before the ejection as seen by the tissue Doppler. In stretch, this should mean that there has to be initial stretch of the apex during the pre ejectioon, simultaneous with shortening of the midwall and base.





Comparing this with basal velocities, we see that the anterior motion of the apex starts in the pre ejection phase. The basal pre ejection spike, however, reaches peak before the apex velocity, which peaks close to the time of start ejection (B), by the tissue Doppler curves. Backward apical motion starts a little before end ejection (C), while end of backward apical motion is well within the early filling phase (D)
Relation between apical and basal  displacement shows the same. Looking at strain rate, at the time of pre ejection, there is maximal apical velocity and there seems to be positive strain rate (stretch) in the apex, but negative strain rate (shortening) in the midwall and base, consistent with there being active pre ejection shortening, but the apex being stretched due to the A-wave impact.




Recordings from two different normal subjects, showing basal and midwall shortening during the pre ejection velocity spike, consistent with active contraction during this phase, while the apex shows stretch, consistent with passive motion of the apex, which may originate from the impact of the A-wave as suggested above. Looking at the early ejection phase, there is an early velocity spike which probably is due to recoil force as discussed above. The early ejection velocity spike can be seen to be progressively dampened from base to apex, as the apex of course cannot be accelerated, being already in contact with the chest wall. But this means higher (absolute) strain rate during early ejection (not to be confused with peak strain rate).


Colour M-modes shows the same, with pre ejection stretch in the apex, and highest absolute early compression in the apical part.

During early ejection there is thus an acceleration of the ventricle due to recoil from ejection. But as the apex is in contact with the chest wall, and cannot be accelerated by this. thus, the apex has to be compressed as shown above, meaning that there is passive compression in addition to active contraction in the apex. This means the shortening during the early ejection (not pre ejection) velocity spike is highest in the apex. However, this is before peak strain rate, and do not necessarily reflect the distribution of peak strain rate.

Delayed and prolonged apex beat can also be demonstrated by tissue Doppler:

Delayed and prolonged (heaving) apex beat in a patient with hypertrophy due to hypertension.

Global systolic function measures


Peak systolic versus end systolic measures of ventricular function.

Peak systolic measures are the measures of peak ventricular performance, and are basically
  • peak ejection velocity in the LVOT,
  • peak annular systolic velocity, and
  • peak global ventricular strain rate.
These occur early in systole, and may be less load dependent, as maximum afterload is reached later in systole. They all occur during the first part of systole, and thus are more closely related to contractility, and especially to contractility changes, as shown in studies (78, 79, 80, 223).

All such studies are really studies in contractility changes, and thus, useful to separate contractile states, rather than measure contractility direct.

However, they are not completely load independent, as increased load will result in a delayed and blunted development of force and velocity, as opposed to the pressure/volume relation.


End systolic measures on the other side, are measures of the total work performed by the left ventricle during ejection. This is influenced not only by force, but also by load (resistance), and the ejection time (HR). They are
  • stroke volume,
  • Ejection fraction (and fractional shortening)
  • annular displacement and
  • global strain

There is, however, little evidence directly comparing displacement / strain to velocity / strain rate at varying load, and the few and small studies that are published seems to indicate a very similar load response. However,  increased contractility will not to the same degree lead to increased stroke volume, if there is no concomitant increase in venous return, as in inotropic stimulation. Thus stroke volume wil be maintained, but at a lower end diastolic volume. This means end systolic measures will be less sensitive to  contractility increase as discussed above (223).


Peak systolic annular velocity (S'), which is early systolic,  compared to peak annular displacement (MAPSE), which is end systolic. S' is actually the peak rate of annular displacement, and is thus closer to contractility, while MAPSE is end systolic and thus closer to ejection fraction.  Peak strain rate, being early systolic,  compared to peak strain, which is mainly end systolic, and closer even, to ejection fraction.


Most of the indices above have been studied, and are established as indices of ventricular function. However, in addition to they all being only imaging indices, they have different shortcomings, and to some degree slightly different interpretation physiologically.

Even LV elastance is an end systolic measure, although it is taken as the real contractility. This may be only in relation to volume, in fact.

Peak systolic measures - contractility indices

Even though contractility per se cannot be measured by imaging alone, the measurement can be approximated, but early systolic measures come close (78, 79, 80, 223).

Peak annular systolic velocity

Peak systolic velocity (S') was early validated as a measure of systolic function (37, 38, 39, 40). Peak annular velocity occurs early in systole, and may be less load dependent, as maximum afterload is reached later in systole. The peak velocity is taken as an average measure of two or four points around the mitral ring.



Pulsed tissue Doppler of the mitral ring.  These are the velocity traces of the longitudinal motion, while dividing by the end diastolic length results in an approximation to the Lagrangian strain rate .
Age dependent peak systolic, early and late diastolic velocity in normals from the HUNT study (165). The early diastolic velocities are higher than the systolic, and the decline is thus steeper, but the relation is evident.

The peak systolic annular velocity is useful in that it is a better marker of systolic function than EF, and that it offers a measure that allows direct comparison of systolic and diastolic function.
as they are measured by the same method.

But there are some slight limitations:

1: Peak systolic velocity is not a direct measure of peak rate of shortening.

Even though it seems intuitive, the comparison with peak strain rate shows that there is a velocity component in the peak that is a global translational motion toward the apex as discussed here. This is due to the recoil force from the ejected blood.


Peak velocities from the myocardial wall are shown in blue and green, showing parallel velocity curves at peak, thus identifying the velocity as translation, which do noe show in the difference (strain rate) curve (red).
Peak velocities along the septum, showing a slight blunting of the velocity peak in the apex. Even if there is a translational velocity, this will decrease in the apex where the myocardium is pressed into the chest wall. The strain rate curves corresponding to the regions between the velocity curves are shown below, indicating the this velocity is not the true deformation rate.


It might be argued that the recoil velocity is also generated by myocardial contraction, and represents a liberation of the work done during IVC. From this argument, peak velocity might be considered a fully legitimate measure of myocardial performance, maybe even more legitimate that peak rate of volume decrease.


2: Peak systolic velocity is not always simultaneous in all segments of the mitral annulus. 

The normal pattern of annular velocities varies in the normal subjects:




A fairly common pattern is a sharp peak in the lateral annulus (cyan), and a more rounded curve with a later peak velocity in the septum (yellow). Thus, the divergence of the curves in the initial ejection phase may represent a light tilting (rocking) of the apex toward the septum. A slightly different normal pattern where the initial peak in the lateral wall decelerates slightly, the accelerates again, giving a later second peak. The septum shows an even curve, but with peak velocity between the two peaks of the lateral wall.
In this case peak annular velocity is early and simultaneous in both walls.

The varying timing of the peaks is most probably due to different impact of the recoil force from ejection, creating a slight rocking motion of the whole heart. AS in the example to the left, this will mean that the lateral peak is exaggerated due to rocking, while the early septal velocity is blunted, and the later peak is due to this blunting.



The impact of the recoil momentum on the septal and lateral annulus will, of course, depend on the angle between the momentum vector (velocity vector), and the ventricular long axis. As the aortic opening is situated in the septal part of the LV base, the angle deviation, if any, can be expected to be towards the septum, delivering the highest impact laterally. This is in accordance with clinical observation, the peak is most consistently present in the lateral wall. However, the ejection from the right ventricle must also be taken into consideration, being nearly simultaneous, and with the same stroke volume (mass), only the difference in velocities will account for the difference in momentum. The pulmonary ostium is also situated medially, in front of the aortic, but often with less of an angle deviation. However, the angle will be opposite, and may counteract the aortic momentum.

Thus, both the actual value and the timing of peak systolic velocity can be dependent on the site where it is measured as shown above. This, of course means that the peak annular systolic velocity which is used as a systolic functional parameter, measured either as one site, or as an average, is an approximation, as the timing may differ between sites.

The correlation with EF is weaker than for MAPSE, which is not unsurprising, EF and MAPSE being end systolic measures, and as such measures of the total systolic work, S' is peak systolic, measuring peak systolic performance.




One of the main advantages of tissue velocities is that systolic and diastolic function are measured by the same method. From the beginning, systolic function by EF was compared to diastolic function by mitral flow, equivalent to comparing apples with bananas. This lead to the concept of pure diastolic dysfunction, which has later been shown to be erroneous (202).

The correlation between systolic function S' and diastolic function e* was found in an early study to be 0.6 over a wider range of ventricular function (201), and in the HUNT study (165)with a large number (N=1266) and limited to healthy subjects, the correlation was found to be 0.59.

The correlation reflects among other things, the physiological mechanism that much of the diastolic recoil is due to elastic stored energy from systolic contraction (restoring forces), but also, and most important: that systolic and diastolic function are closely related.




In another study (202) it was found that the systolic function by S' was reduced in patients with heart failure with normal ejection fraction. This led to a renaming of the state that up to then was called "diastolic heart failure" to "heart failure with normal ejection fraction". This, of course corrects the implied, but mistaken assumption that there existed a pure diastolic failure. However, it does not address the fundamental problem, which is one of methodology, that EF should not been used in normal sized or smaller ventricles.


The S' has been shown to be sensitive for reduced function in relatives who are mutation positive, of patients with manifest hypertrophic cardiomyopathy, despite having normal EF and no hypertrophy (203). The diastolic function by tissue Doppler was similarly decreased. It also correlates better with BNP in heart failure than the fractional shortening (204).

Thus, the peak systolic annular velocity is useful in that it is a better marker of systolic function, and that it offers a measure that allows direct comparison of systolic and diastolic function.
Where and how should measurements be done?



As the peak velocities are more often higher in the lateral than the medial, it is evident that the measurements are different if different sites are chosen. This can be seen from the HUNT study (165). This study consisted of  673 women with a mean BP of 127/71 ,mean age of 47,3 years and BMI of 25.8 and 623 men, with mean BP of 133/77, mean age of 50.6 and BMI of 26.5. Both sexes were normally distributed with an SD of 13.6 and 13.7 years, respectively. 20% of both sexes were current smokers. Basic echo findings  are in accordance with other studies, like the findings of Schirmer et al (156, 157), so the study population may be assumed to be representative.



Anterior
(Antero-)lateral
Inferior
(Infero-)septal
PwTDI S' (cm/s)
8.3 (1.9) 8.8 (1.8)
8.6 (1.4)
8.0 (1.2)
cTDI S' (cm/s)
6.5 (1.4)
7.0 (1.8)
6.9 (1.4)
6.3 (1.2)
Results from the HUNT study with normal values based on 1266 healthy individuals. Values are mean values (SD in parentheses). 

The maximal differences can be seen to be about 10% relative, with the highest values in the lateral wall, lowest in the septum. The reason for this, can be partly explained by the differences in length of the walls, seeing that the peak strain and strain rate varies much less.

The initial studies (37, 38, 39) used the average of four sites as a measure of global systolic function. In the HUNT study, however, there were no difference between the peak systolic velocity (S') mean of lateral and septal, and the mean of all four points. However, Thorstensen et al (154) did show that reproducibility was about 35% better using four point average (p<0.001), in line with what was found earlier (40), even if the mean values were the same.


The common method of measuring peak velocity at each point and then average the peak values from two or four point, is methodologically slightly unsound, as they may not be simultaneous:

Septal (yellow) and lateral (cyan) velocity curves from the fisrt subject above. Peak velocities are 6.25 cm/s septally and 7.6 cm/s laterally. Mean of peak values are thus 6.93 cm/s. The averaged curve of the two is shown in red, and the peak of the average is 6.67 cm/s. Difference here is small, but this may not always be the case.

The point from a puristic view is that if the peaks are not simultaneous, the mean peak velocity doesn't exist in real time (cfr. the peak-to-peak gradient of invasive aortic stenosis measurement). Still, the method has been established as useful, and normal values for the averages has been established (165). And, as in the example above, while the early peak in the lateral wall is exaggerated due to the rocking, the early septal velocity is blunted. The true peak translational velocity is seen in the average curve, and the true peak velocity is the peak of the average curve, not the average of the peaks.

The varying timing of the peaks is most probably due to different impact of the recoil force from ejection, creating a slight rocking motion of the whole heart. AS in the example to the left, this will mean that the lateral peak is exaggerated due to rocking, while the early septal velocity is blunted, and the later peak is due to this blunting.

In some cases, the rocking of the apex, even if the ventricle is normal may become completely misleading.





Rocking heart with normal ventricular function.
Peak velocities have totally different timing, and much of both of the peak components are due to translation.The septal peak has a component of rocking to the right, the lateral peak a component of rocking to the right, both may be overestimates.
As discussed here. In this case, the peak velocities should be viewed with skepticism as functional measures. The mean curve might give a more correct estimate, although this is not validated, and is not available in standard analysis software.

Using pulsed wave tissue Doppler, this is not an option, and curve averaging is not standard analysis software.

Normal values for systolic velocities of the right and left ventricle from the HUNT study by age and gender. From  (165).


Left ventricle, mean of 4 walls
Right ventricle (free wall)

S' (pw TDI)
S' cTDI
S' (pwTDI)
Females



< 40 years
8.9 (1.1)
7.2 ( 1.0)
13.0 (1.8)
40 - 60 years
8.1 (1.2)
6.5 (1.0)
12.4 (1.9)
> 60 years
7.2 (1.2)
5.7 (1.1)
11.8 (2.0)
All
8.2 (1.3)
6.6 (1.1)
12.5 (1.9)
Males



< 40 years
9.4 (1.4)
7.6 (1.2)
13.2 (2.0)
40 - 60 years
8.6 (1.3)
6.9 (1.3)
12.8 (2.2)
> 60 years
8.0 (1.3)
6.4 (1.2)
12.5 (2.3)
All
8.6 (1.4)
6.9 (1.3)
12.8 (2.2)
Annular velocities by sex and age. Values are mean (SD).  pwTDI: Pulsed Tissue Doppler recorded at the top of the spectrum with minimum gain, c TDI: colour TDI.  Normal range is customary defined as mean ▒ 2 SD.

The study is based on 1266 healthy individuals from the HUNT study by Dalen et al (165). The age dependency of values is evident. Colour tissue Doppler gives mean values, which are consistently lower than pulsed wave values, as discussed here. It is evident that the systolic values decline with age, as do the early diastolic.

It is important to realise that the peak values obtained by pw tissue Doppler are higher, due to the breadth of the spectrum, while colour tissue Doppler gives mean velocities, thus being modal velocities in the middle of the spectrum. However, peak values by spectral Doppler are affected by gain settings (increased gain - broader spectrum - higher peak values), while colour Doppler are affected by clutter (stationary reverberations - zero velocity - reduced average).



Same tissue Doppler recording with two different gain settings. We see that peak systolic velocity differs by 2 cm/s, and the lowest gain setting is closest to the modal velocity. However, the modal velocity itself, remains unchanged by the gain setting.
There is a band of clutter close to zero velocities, but as seen here, the spectral modality makes it very easy to separate the true and clutter velocities. However, the clutter affects the autocorrelation velocity (red line), giving lower velocities, but with clutter filter this effect is removed (blue line), and the peak value is substantially higher. Image modified from (268).


Peak acceleration (??)


As acceleration precedes velocity, and is at the time of peak rise of velocity, this should be slightly earlier than peak velocity, and thus even less load dependent, - at least afterload, preload dependency will still be present. Acceleration is also more closely related to peak force by Newton's second law (F = ma). In addition, if taking the peak velocity to be partly a function of the recoil, it is also caused by the pressure buildup, even more so than the peak velocity. Thus there are hypothetical advantages in relation to physics and physiology.

However, the concept is ill defined. Also, the temporal derivation of acceleration from velocity will result in a less favourable signal-to-noise ratio than the velocities.



Velocity curves from a normal subject. The initial peak acceleration may be defined by the slope of the tangent to the initial velocity curve. As illustrated, as the two curves from septum and lateral walls are different, this will result in different acceleration values. In addition, there can be different ways of defining the tangent:
  • A: The steepest slope of the lateral curve
  • B: The slope from nadir to the lateral curve peak
  • C: The steepest slope of the septal curve
  • D: The slope from nadir to the septal curve breakpoint
  • E: The slope from nadir to septal curve peak
All of them reasonable, but resulting in wildly different values (This is equal to a noise component as shown right)
Real-time temporal derivation of the two velocity curves. Due to the derivation, the curves are fairly noisy, especially taking into account the the velocity curves was somewhat smoothed at the outset. It is obvious that the peak values may be affected by the noise,  incorporating noise spikes. Averaging the septal and lateral points, still doesn't solve the noise problem. Also averaging can be done in two ways:
  • Mean of peak values, which in this case will be 186, and
  • Peak of mean curve, in this case 163
And in addition, curve derivation and averaging is not standard issue in analysis software.

At present, the peak acceleration is less useful, being
  • Closely related to peak velocity, as the peak velocity is determined by the rate of velocity rise,
  • In need of definition of concepts
  • Dependent on heavy post processing, and not standard analysis software
- while especially pw Tissue Doppler in the standard mode is a quick, robust and online method.


Peak systolic strain rate

Peak systolic strain rate is the peak rate of shortening. As explained above, this peak occurs later during the ejection phase than peak velocity, as the strain  rate algorithm subtracts the initial velocty peak, being translation, not deformation:





Examining one normal subject with early velocity peak in the lateral annulus:
Looking at velocities within the wall in base an apex, the biphasic pattern with an early peak can be seen in both points in the lateral wall.
Examining the strain rate from the entire walls between the apical and basal points no sign of a biphasic shortening can be seen, indicating that the lateral peak is only due to translation, the peak being subtracted. The peak strain rate is much later than peak velocity in both walls.


The slight rocking motion affecting the timing of peak velocities, means that there is no fixed relation between the timing of peak strain rate and peak velocity:




Early peak velocity on both sides. Slightly later peak strain rate in both walls.
Early lateral peak velocity. late septal; early septal peak strain rate, later lateral, mean peak strain rate later than mean peak velocity
Early lateral and later septal peak velocity, earlier lateral than septal peak strain rate, mean peak strain rate later than mean peak velocity.



Thus, peak strain rate is the true measure of peak deformation rate, i.e. peak rate of shortening. However, this does not mean that it is a truer measure of peak systolic performance, as the peak velocity incorporates the ejection recoil due to the isovolumic pressure buildup.

But basically, as volume change is generally are related to longitudinal shortening, peak strain rate must be close to peak rate of volume reduction, i.e. peak emptying rate.

For global strain rate measures, the strain length as well as the ROI should be as long as possible to reduce noise (331) as shown in the above examples and discussed in the measurements section.

Thus, the peak strain rate should be more related to peak force than to peak rate of force development. However, in an experimental invasive study, Greenberg (80) found a stronger correlation between both dP/dt and LV elastance with strain rate than with systolic annular velocities.

Normal values are necessary if measurements are to be used diagnostically. In addition, they will give additional information about physiology. In the north Tr÷ndelag population (HUNT) study, 1266 subjects without known heart disease, hypertension and diabetes were randomly selected from the total study population of 49 827, and subjects with clinically significant findings on echocardiography (a total of only 30) were excluded. (153) This is the largest normal population study of echocardiographic strain and strain rate rate to date. End systolic strain and peak systolic strain rate was measured by the combined tissue Doppler / speckle tracking segmental strain application of the Norwegian University of Science and Technology, but the results were compared to other methods in a subset of subjects, showing small differences. The study consisted of  673 women with a mean BP of 127/71 ,mean age of 47,3 years and BMI of 25.8 and 623 men, with mean BP of 133/77, mean age of 50.6 and BMI of 26.5. Both sexes were normally distributed with an SD of 13.6 and 13.7 years, respectively. 20% of both sexes were current smokers. Basic echo findings  are in accordance with other studies, like the findings of Schirmer et al (156, 157), so the study population may be assumed to be representative.

While differences between septum and lateral wall was of the order of 10% in velocities, in deformation parameters (153), the same difference was on the order of 4% in strain rate and only 1% (relative) in strain.

Normal values for strain and strain rate per wall in the HUNT study. From (153).


Anteroseptal
Anterior
(Antero-)lateral
Inferolateral
Inferior
(Infero-)septal
SR (s-1)
-0.99 (0.27) -1.02 (0.28)
-1.05 (0.28)
-1.07 (0.27)
-1.03 (0.26)
-1.01 (0.25)
Strain (%)
-16.0 (4.1) -16.8 (4.3)
-16.6 (4.1)
-16.5 (4.1)
-17.0 (4.0)
-16.8 (4.0)
Results from the HUNT study (153, 165) with normal values based on 1266 healthy individuals. Values are mean values (SD in parentheses).  The differences between walls are seen to be smaller in deformation parameters than in motion parameters, although still significant due to the large numbers.

Normal values for global strain and strain rate in the HUNT study by age and gender. From (153).


Female
Male

End systolic strain (%)
Peak systolic strain rate
End systolic strain Peak systolic strain rate
< 40 years
-17.9% (2.1)
-1.09s-1 (0.12)
-16.8% (2.0)
-1.06s-1 (0.13)
40 - 60 years
-17.6% (2.1)
-1.06s-1 (0.13) -18.8% (2.2)
-1.01s-1 (0.12)
> 60 years
-15.9% (2.4)
-0.97s-1 (0.14) -15.5% (2.4)
-0.97s-1 (0.14)
Over all
-17.4% (2.3)
-1.05s-1 (0.13) -15.9% (2.3)
-1.01s-1 (0.13)
  Values are given as mean ( SD). The customary definition of normal values as mean ▒ 2SD, giving about 95% of the normal population, results in wider normal limits than previously shown as cut off values in small patient studies. The values were normally distributed, and with no clinically significant differences between levels or walls. Values decline with age, as does the velocity.



Normalised velocity(?)

As seen later, peak annular displacement can be normalised for left ventricular length to derive a measure of global longitudinal strain. But this doesn't necessarily mean that normalising velocity in the same way gives global strain rate. Assuming that annular velocity was the peak rate of ventricular shortening, normalising for end diastolic length would give peak Lagrangian strain rate, normalising for instantaneous systolic length would give the Eulerian strain rate. However, giving the difference in riming between the two curves, due to the translational velocity, this is not the case.



Basal velocity traces, and the velocity traces normalised for end diastolic ventricular length (Lagrangian normalisation), results in curves that resemble inverted velocity curves, with the same shape.
Comparing this with the real velocity / strain rate plots from the same subject, it is evident that strain rate curves have a different shape. (In fact, in this case the lateral strain rate curve is more rounded, the septal with an earlier and more defined peak, opposite of the velocity curves).

This means that in terms of curve shape and timing, there is no point in normalising the velocity curves, and the normalised velocity curves is still a slightly different measure than strain rate.


However, where there is a large variation in ventricular size, as in children it makes sense, giving age independent measures  (159, 214, 288). Strain rate is one form of size normalising, but using pulsed tissue Doppler, normalised velocity will make the velocity measurements useful in children of all ages.


Basically, peak strain rate is most useful for assessing regional function, where the motion due to tethering to neighboring segments needs to be subtracted n(although the effect of segment interaction remains). With uneven segmental contractility, the peak strain rate in different segments also becomes non simultaneous.

Peak ejection velocity

LVOT ejection velocity must be proportional to flow, as the LVOT diameter is considered constant. But this means that peak systolic velocity is actually a direct measure of peak volume reduction rate or peak emptying rate. And, as peak shortenoing rate (strain rate) is very close to peak emptying rate, this means that both measures are very close to measuring the same thing. THis was evident in a study where both measures did show a very similar change with chenges in contractile states (223).







In all four subjects, the peak velocity of LVOT flow seems to be relativelt simultaneous with peak strain rate, consistent with theory. Averaged curves might be even closer.

Thus, both theoretically, empirically and experimentally, the peak LVOT flow and peak global strain rate seems to be measuring very much the same event, even though indifferent measures.

But should peak LVOT velocity be normalised for heart size? Probably not, AS strain arte already is a norlmalisation for heart size, the flow velocity is dependent on LVOT diameter, whic increases with heart sise. So, the LVOT velocity is in a way a normalisation of peak flow.

Normal peak ejection velocities from Doppler, by age and gender from the HUNT study (165)


Females
Males
< 40 years 1.01 (0.17)
0.99 (0.17)
40 - 60 years 1.02 (0.16)
0.99 (0.18)
> 60 years 1.01 (0.17)
0.96 (0.18)
Over all 1.01 (0.16)
0.98 (0.18)
Values are given as mean ( SD). The customary definition of normal values as mean ▒ 2SD, giving about 95% of the normal population, results in wider normal limits than previously shown as cut off values in small patient studies.

The only difference is that peak values of peak ejection velocity do not decline with age. AS stroke volume gpoes down with ventricular volume by age, this must mean a corresponding reduction in LVOT diameter.



With the appearance of new methodology, a number of new methods for measuring left ventricular global function has emerged. Older measures has traditionally been measurements of the cavity function: Stroke volume, ejection fraction (and the M-mode equivalent shortening fraction). Newer methods include longitudinal measures of wall function, as annular displacement and velocity, as well as mean strain/strain rate, either based on segmental measurements, or a global averaging (as global strain form speckle tracking 2D strain). It should be of general interest to comment on the relationship between the methods. It is also important to realise that while strain and strain rate are measures of shortening per length unit, the annular velocity and displacement are also measures of the same, but in absolute values (i.e. not normalised for ventricular length). However, all measures that measure relations to changes, i.e. in paired experiments of load alterations, the normalisation will cancel out, and displacement will behave as strain, strain rate as velocity. Thus all experiments with systolic displacement and velocity in relation to global changes, will pertain also to strain and strain rate.




End systolic measures - systolic work indexes.


End systolic measures on the other side, are measures of the total work performed by the left ventricle during ejection. This is influenced not only by force, but also by load (resistance), and the ejection time (HR). They are
  • stroke volume,
  • Ejection fraction (and fractional shortening)
  • annular displacement and
  • global strain

There is, however, little evidence directly comparing displacement / strain to velocity / strain rate at varying load, and the few and small studies that are published seems to indicate a very similar load response. However,  increased contractility will not to the same degree lead to increased stroke volume, if there is no concomitant increase in venous return, as in inotropic stimulation. Thus stroke volume wil be maintained, but at a lower end diastolic volume. This means end systolic measures will be less sensitive to  contractility increase (223).

Cavity measurements of systolic function


Fractional shortening

As M-mode was the first echo modality, the fractional shortening of the LV cavity was the first LV systolic functional measure by echo. The fractional shortening is defined as FS = (LVIDD - LVIDS)/LVIDD thus, in fact being an one-dimensional version of EF. Diameter is conventionally measured to the endocardium, so the fractional shortening is more precisely the endocardional fractional shortening. It's less accurate than the EF when there is regional dysfunction, as the measured fractional shortening will be generalised to the whole ventricle. It is quite common to measure longitudinal strain, i.e. wall or segment shortening as a measure of longitudinal function. On the other hand the fractional shortening of the chamber diameter is a well established measure of global and radial function. But in the case of hypertrophy, this may lead to completely erroneous conclusions about the changes in radial versus global function, as shown in the theoretical treatment below.

The relation between wall thickening and fractional shortening is ilustrated below:


In this theoretical M-mode of the LV, a normal ventricle has a wall thickness of 1 cm, an internal end diastolic chamber diameter (EDD) of 4 cm, resulting in an external diameter of 6 cm. As most of the wall thickening is inward, with little change in outward diameter (except in the case of differing filling pressures on the two sides), an end systolic wall thickness of 1.5 cm will result in a diameter shortening of 1 cm and an end systolic chamber diameter of 3 cm. Thus, wall thickening (WT, transmural strain) is (1.5 cm - 1 cm) / 1 cm = 50%, chamber diameter reduction is 1 cm, fractional shortening (FS) is (4 cm - 3 cm) / 4 cm = 25%. Thus, if wall thickening decreases due to reduced myocardial function, so do fractional shortening as seen in the middle figure. And if there is dilation as well, the denominator will increase, resulting in further reduction in FSas an inverse function of the diameter. In LV dilation, there is usually a combination of increased diameter and reduced wall thickening.


The erroneous comparison between longitudinal strain and fractional shortening:

The incompressibility principle tells us that as the wall shortens in the longitudinal and circumferential direction, it has to thicken in the transverse direction, and the relation is geometrically determined. Thus the longitudinal and transverse function as measured by strain should be interrelated. Reports about radial compensation of reduced longitudinal function is in direct opposition to the incompressibility principle.  The problem arises if we do not measure the same values for longitudinal and radial function.


Compared to the normal example to the left,  in the case of concentric hypertrophy as in the middle, the chamber diameter is reduced due to increased wall thickness.  A hypertrophy leading to a wall thickness of 1.5 cm, will give an EDD of 3 cm. A systolic wall thickening of  0.5 cm will then be (2 cm - 1.5 cm) / 1.5 cm = 33%; i.e. a clear reduction in radial function. But 1 cm diameter shortening  is FS = (3 cm - 2 cm) / 3 cm = 33%, an apparent  increase in radial function, due to geometrical misconception! In concentric remodelling (right), the diameter is reduced. In the case of heart failure with reduced myocardial function, (reduced wall thickening), the diameter reduction may cause the FS to be normal, despite the reduced radial function.


From the reasoning above, any conclusions about radial function based on fractional shortening in the presence of hypertrophy may be erroneous, and the term radial function needs to be defined. The conclusion that there is radial compensation for reduced longitudinal function should be reserved to the cases where WT is increased (If this is possible, it seems theoretically impossible, as the reduced longitudinal shortening should correspond to reduced wall thickening due to incompressibility).

It is extremely important that if longitudinal and "radial function" are compared, care should be taken that the measurements are comparable. To compare for instance fractional shortening of the LV diameter with longitudinal strain (wall shortening), is comparing two different measures, and may lead to completely erroneous conclusions as shown above, where fractional shortening increases but wall thickening decreases.

 as the same erroneous results will be obtained by the fractional shortening as of EF, as shown below.

And this shows that fractional shortening is not a true measure of "radial function".


Patient with concentric hypertrophy. Looking at the cavity, the systolic function may appear fair.





Wall thickness 17 mm, EDD 40 mm, Fractional shortening was 35%, however, wall thickening only 28%





Ejection fraction

Based on Nuclear or X-ray contrast studies, the first measures was measurements of cavity reduction in systole, i.e. the stroke volume. While this may be the most important result of cardiac pumping, it confers little information about the state of the heart itself. A dilated ventricle can maintain stroke volume, but it is reduced in terms of the left ventricle volume, and may have a severely reduced contractility. Thus stroke volume should be normalised for end diastolic volume, to obtain Ejection fraction:

Ejection fraction is still the most widely used measure of systolic left ventricular function today. This is mainly due to the vast amount of prognostic information from earlier studies, and the prognostic interventions that are geared to a cut off point in EF. Even so, EF has been shown to be a poor prognosticator even in heart failure, when patients without dilation is included (227). In assessing EF, it should be emphasized, however, that EF is not a direct measure of myocardial function, as it measures the cavity, not the myocardial deformation. At best, it could be characterised as an indirect measure. Does this matter? Yes. If we look at a few examples:

Again, the cavity approach works very well in dilated hearts, but not in eccentric hypertrophy:


Classic view of ejection fraction. In a dilated ventricle (right), with thin wall, both wall thickening and longitudinal shortening are reduced. The cavity volume is increased, so the EF is reduced, even if the stroke volume may be maintained. As the ventricle dilates crosswise, the stroke volume is maintained with a shorter MAPSE, thus the longitudinal strain is also reduced, as shown below.

As we see, in dilated ventricles, there is a correlation between longitudinal shortening and EF, as explained below. However, this correlation is not present in hypertrophic ventricles (190). But this is due to the fact that in concentric geometry (hypertophy or remodelling) EF doesn't measure systolic function at all.

The erroneous use of EF in concentric geometry.

concentric geometry, EF will not give true measures of systolic function at all!


In concentric hypertrophy (middle), as often seen in pressure overload, the wall may be thickened, and the cavity volume is usually reduced.

Concentric hypertrophy reduces the cavity volume. Absolute wall thickening may often be preserved, while relative wall thickening is reduced as in the example of rectional shortening above. Then the longitudinal shrtening will also be reduced. I have pointed this out concerning fractional shortening as seen above, the reasoning was taken further into three dimensions by MacIver (228). EF has been shown to be more related to absolute than relative wall thickening (229), and  may be unchanged or even increased, but stroke volume is reduced, which also indicates systolic dysfunction. This is the same finding as in FS.


The same patient as above. EDV about 100 ml, EF about 55%. Again the systolic function may appear normal, looking only at the cavity. However, looking at long axis shortening, it appears severely depressed.


- which is confirmed, systolic mitral annular excursion is 5 mm and peak systolic annular velocity is < 3 cm/s


In concentric remodelling, as in the atrophy of ageing, where LV mass is unchanged. but ventricle size is reduced, the EF will fare just as poorly. Wall thickness may be unchanged or increased, but as the myocardial mass/volume is reduced less than cavity size, the myocardial wall / cavity volume ratio is decreased. Again, stroke volume is reduced, EF may be normal. Absolute wall thickening may be reduced, but relative wall thickening more, and the longitudinal shortening is reduced in proportin to relative wall thickening.

The annular displacement has been shown to be more sensitive than EF in predicting events in heart failure (36, 192) and hypertension (193).
But alas, interventional studies using echocardiography as secondary outcome, persists in using only EF, instead of including newer measures for direct comparison of the ability in predicting clinical outcome as well as establishing cut off values for intervention, as studies are driven by investigators with little knowledge of echocardiography. This is illustrated below.


Normal left ventricle
Dilated left ventricle
Concentric hypertrophy
Concentric remodelling

Diastole
Systole
Diastole Systole Diastole Systole Diastole Systole
LV length (cm) 9.5
7.7
11
9.8
11
10.6
8.5
7.8
LV outer diameter (cm) 6.0
5.7
7.5
7.1
6.5
6.18
4.5
4.2
Wall thickness (cm)
0.95
1.43
0.6
0.7
1.7
2.0
0.95
1.2
LV Inner diameter (cm) 5.1
4.1
6.3
5.7
3.1
2.1
2.6
1.9
LV cavity volume
123
78
228
167
55
24
30
15
Stroke volume (ml)

45

61

31

15
Ejection fraction (%)

62

27

56

51
Fractional shortening (%)

30

10

32

27
Wall thickening (%)
50

20

20

25
Longitudinal shortening (%)

21

10

3

8


15

7

14

13
All measures are calculated from a geometrical model of a half ellipsoid with wall thickness in the apex being half of the sides, all measures are calculated from the input measures of LV length, outer diameter, wall thickness and wall thickening.

While cavity parameters are preserved or even increased in the concentric geometry, all systolic wall deformation measures (longitudinal, circumferential and transmural strain)are reduced.

It has been shown by speckle tracking observational studies in various hypertrophic states, that all three pricipal strain may be reduced, whil ejection fraction is preserved (230, 231, 232, 233).


Thus, the EF or FS is a measure that actually only works with dilation of the ventricles and becomes erroneous in the cases of reduced EDV. EF is a geometrical concept, and only works in some geometries.  Asd both the modelling and the sudies cited above shows, the systolic finction may be reduced in all directions despite a normal EF. Because this has been poorly  recognised, it has lead to some fairly bizarre results. As systolic function has been measured by EF, and diastolic function with mitral flow parameters, the hypothesis of "isolated diastolic heart failure" has been proposed. At the outset, measuring systolic and diastolic function by different measures with different sensitivity, is methodological nonsense in any case.

This has been realised, ad the term is now substituted with the term "Heart failure with normal  or prteserved ejection fraction" (HFNEF or HFPEF).

But as EF as a measure of systolic function in the case of small, hypertrophic ventricles is meaningless, the concepts are still dubious, the emphasis of an erroneously normal EF remains.

The problem with both strain AND EF in eccentric hypertrophy

In eccentric hypertrophy, the problem reverses, but in this case it even affects strain. Basically, in eccentric hypertrophy, the VV mass increases, but hte wall cavity ratio remains normal (146). This means that the ventricle enlarges mainly outwards, but as a more or less normally thick wall (at least relative) surrounds a much larger cavity, the mass has to increase. This is seen in different states:

  1. As compensation for volume load in valvular regurgitation. In this case, the end diastolic volume increases, but so does the total stroke volume. In this case the EF remains normal or even super normal. The strains can thus also be expected to remain normal as long as myocardial function is.
  2. In athletes heart. In this case there is eccentric hypertrophy in response to endureance training, i.e. the demands on the ventricle during near maximal performance. The ventricle increases both in diameter and length, and hence, in end diastolic volume.

Diagram illustrating how eccentric hypertophy, with a larger ventricle with normal wall thickness, will show reduced shortening fraction due to the larger denominator, even if wall thickening is normal. (Same wall thickening, larger end diastolic diameter, same absolute, but less relative diameter shortening). The finding will be the same in three dimensions, a larger ventricle with normal strains will still show reduced EF, even if stroke volume remains the same (Larger EDV, same stroke volume = same absolute, but less relative  volume reduction; i.e. lower EF). This, however, is an over simplification, unchanged stroke volume in a larger ventricle will show reduced strains as discussed below.

As long as stroke volume remains constant, the absolute wall thickening and shortenings (strains) will also remain constant, but the relative wall shortening will be less due to a longer ventricle (i.we. lower longitudinal strain). As relative wall shortening decreases, this may be seen to give a lower wall thickening as well, as the two are interrelated due to the incompressibility principle. If the wall thickening is unchanged in terms of absolute amount of wall thickening, the thickening is spread over a larger surface of a longer and wider ventricle, and thus is reduced in terms of relative wall thickening. And in fact in a larger ventricle, even absolute wall thickening may be reduced, as a lower amount of wall thickening wil result in the same volume reduction when spread over a larger surface.

Thus; in eccentric hypertrophy, the strains will decrease, even with unchanged stroke volume.






Eccentric hypertrophy with unchanged stroke volume. In the larger ventricle to the left, the same stroke volume as to the right, can be maintained by a smaller longitudinal shortening (MAE) due to the wider ventricle as explained here. This will result in a lower longitudinal strain. And the strain is even more reduced as this smaller MAE is relative to a greater LV length.  But less longitudinal shortening will also result in less wall thickening, thus all strain are reduced. However, even this is still an over simplification, as this is reasoned without the compensatory regulatory mechanisms.
Thus, with an increased EDV and unchanged stroke volume, the EF and FS may be reduced, and so may strains, due to the larger ventricle.


However, athletes usually have downregulated heart rate as well,  which increases diastolic filling, and thus the stroke volume. In the intact body, the cardiac output is regulated according to the circulatory need, by both autonomic balance and other vasoactive and volume regulatory mechanisms affecting both filling and resistance, contractility and heart rate simultaneously.

This means that athletes at rest (having no need of increased resting cardiac output - only of increased cardiac output reserve) will have unchanged cardiac output, a larger LV, with lower heart rate and increased stroke volume. But as this is a result of a lower sympathetic tone, the ejection fraction and strains may still be reduced, although to a lesser degree than if HR was unchanged, and may be unpredictable.

For evaluation of systolic myocardial function in eccentric hypertrophy, myocardial systolic velocities or strain rate would be more appropriate, although the litterature is fairly scarce, at least in comparing with normals. At least, the rate of shortening should be less affected by the total stroke volume, but afterload may still be a confounder, in general athletes may have lower blood pressure, but also a lower sympathetic tone.

Wall measurements - long axis systolic function.

Wall thickening is a measure of systolic deformation. It can be assessed semi quantitatively in B-mode. Wall motion score index (WMSI) by B.mode, being the  average of wall motion score  of all evaluable segments becomes a measure of  global function, and has been shown to correlate with EF in infarcted ventricles (40). It has also been shown to be similar in sensitivity to reduced function (and infarct size) to global strain (189). However, the index is useless unless there is regional differences. Any dilated cardiomyopathy will show hypokinesia in all segments, giving a WMSI of 2, regardless of EF.
Wall thickening measured in M-mode, however, is only available in limited segments, and can only be generalised to global measures if the ventricle is symmetric. In addition,  the wall thickening is mainly a function of the long axis shortening, due to the incompressibility of the heart muscle.




Systolic long axis shortening

The systolic long axis function is measured by any means of any longitudinal motion or deformation. I.e. Long axis shortening measured by mitral annulus motion or global strain, or shortening velocity / rate by mitral annulus velocity or global strain rate.






It has been established that the longitudinal shortening of the left ventricle, and thus the longitudinal measures is closest related to the stroke volume and EF, i.e. to the total left ventricular volume change (30 - 35, 56, 59, 60, 64 - 67, 116).
Longitudinal systolic strain of the left ventricle is shortening, normalised for diastolic length (similar to EF, which is volume decrease (stroke volume) normalised for end diastolic volume). As longitudinal shortening describes most of the actual ejection work, , there is a strong relation between EF and longitudinal strain. Thus, it may seem that the longitudinal fibres (or force components) are the main contributors to the ejection work, i.e. the isotonic part of the work.

Mitral annular systolic displacement




Long axis shortening of the ventricle equals the mitral annular systolic displacement. Longitudinal M-mode through the mitral ring, displaying the displacement of the mitral ring. The total systolic displacement (MAPSE; mitral annular plane systolic excursion) can be measured.  If  the MAPSE is divided by the end diastolic length of the ventricle (which, in fact is a spatial derivation), it will give a measure of the strain of the wall. The global strain of the left ventricle is an average of more points of the wall. The longitudinal (Lagrangian) strain during systole is thus MAPSE /LD.



Mitral annular plane systolic displacement or excursion (MAPSE), and mitral annular systolic velocities, are measurements of total ventricular shortening and shortening velocity:

Mitral annular dexcursion can be measured by B-mode, M-mode or tissue Doppler:



MAPSE by M-mode. In this case the MAPSE was 14 mm in the septal site and 16 mm in the lateral, giving an average of 15.
MAPSE by tissue Doppler showing an MAPSE of about 15 mm.


The annular measurements reflect the total shortening of the ventricle, and are thus measures of global longitudinal function.

The mitral annular systolic descent has had many names: The mitral annular excursion (MAE) (31, 35, 37, 40) has been used for a long time. Atrioventricular plane descent (AVPD) (30, 32, 34, 36) is incorrect, as the term also comprises the tricuspid part, and while tricuspid displacement and velocity can be measured (and is higher than in the left ventricle) , it is usually measured only in one point, and the relative weights for the measurements is unclear.

However, the term TAPSE for the tricuspid systolic annular excursion has been firmly established. In order to remain consistent in nomenclature, the corresponding term MAPSE for Mitral Annular Plane Systolic Excursion is in increasing use. Thus, it might be the best term, and it still retains the specificity that AVPD lacks.

The longitudinal shortening has been shown to be very closely related to ejection fraction when comparing different patients with normal or reduced left ventricular function (30, 31, 32, 34, 35, 36, 40, 64), as illustrated below:


When the left ventricle dilates, the volume increases, and the stroke volume can be maintained by a smaller fraction (Ejection fraction) of the total (end diastolic) volume. At the same time, the cross sectional area increases, so the volume can be maintained by a smaller stroke length. 

The relation between MAPSE and EF has shown a correlation of 80 - 90%. However, the relation only holds in dilated ventricles. In normal ventricles, the MAPSE is related to the stroke volume (59, 60, 116). In left ventricular hypertrophy, the MAPSE is reduced despite preserved EF, and there is no correlation (190).

In addition, the MAPSE is reduced in ventricles with normal ejection fraction , the so-called HFNEF (191), i.e. despite normal ejection fraction. 

The annular displacement has been shown to be more sensitive than EF in predicting events in heart failure (36, 192) and hypertension (193), indicating that it is a more precise measure of systolic function, that the cavity measurements. This may be due to the shortcoming of EF in small ventricles / hypertrophy. There is also a trend towards a better correlation with infarct size than EF (150).

Also, the MAPSE correlates better with BNP in heart failure, that the fractional shortening (204).

Thus, the MAPSE is a more all round useful measure of longitudinal function than EF.

There has been some arguments for measuring MAPSE only during ejection, i.e. excluding the isovolumic phases (194). The value will be a little lower, and the main advantage seems to be that post systolic shortening, not being part of the systolic work, will be eliminated.


Systolic annular displacement of the septal point. There is a small shortening in the isovolumic contraction phase (IVC), and post systolic motion (PSM) after AVC, so the systolic MAE is lower than the total MAE.

However, the total shortening is probably related to the total ventricular size. This means that small ventricles has a lower MAPSE, even if similar in relation to the total length. This also means a lower stroke volume, of course, from a smaller ventricle. So the relation MAPSE x cross sectional area = SV still holds. However, this means that some of the variations in MAPSE are due to heart size, not heart function, which mans that the relation with heart function has a reduced explained variance. Theoretically, this means that the annular displacement should be normalised for heart size, which also is the case when using global strain instead, being relative shortening. This is definitely necessary in children (159, 214, 288), where the varation in heart size is great, the advantage in adults, where variation in heart size is less (and less than the difference betweeen normal and pathological) is not documented.

Where should measurements be done?
As the displacement is higher in the lateral than the medial, it is evident that the measurements are different if different sites are chosen. All studies have used the average of four points: septal and lateral in the four chamber view, and anterior and inferior in the two-chamber view. Thus the average is fairly robust, representing a global average. However, the main reason for using four points would be to reduce variability (which is reduced by about 25% by using four points instead of one (40). In addition, regional differences due to regional dysfunction may be evened out,, however, we found that ring motion was reduced in all points in localised infarcts (40).



Normalised displacement.


Both annular displacement (MAPSE) and annular systolic velocity can be normalised for (divided by) the length of the ventricle or wall.  


Systolic strain is normalised MAPSE. The normalised MAPSE for this ventricle with an end diastolic length of 9.2 cm and an MAPSEE of 15 mm is 15 / 92  = 16.3. THis corresponds to a longitudinal strain of -16.3%. Compare with global strain, in this case the global strain was 16.1%, giving a good comparison. However, the two methods are different, as this method normalises for the length of the curved wall, and the actual values are dependent on the curvature (especially in the apex) of the segments.

However, there is so far no agreement of how this normalisation should be done. It is evident that the shortest length is the mid length of the ventricle as seen above. Strain on the other hand, is a myocardial measure, and should be measured along the myocardium, i.e. wall length. But as shown below, this can be done in various ways. In relation to M-mode or tissue Doppler, the natural measure might be along a straight line from apex to the mitral annulus. In relation to speckle tracking, however, there may be possibilities to measure along the wall. But still there is a choice between midwall and endocardial. And finally, the normalisation of MAPSE makes the new parameter much more sensitive to foreshortening.



Diastolic and systolic images of the heart. Systolic shortening of the left ventricle relative to diastolic length, is the systolic strain of the ventricle.  The longitudinal strain during systole is thus:

However, it is also evident that as the wall shortens, it also thickens, to conserve the volume. Heart muscle is generally assumed to be incompressible.
Strain being (L - L0) / L0 may still not be unambiguous, as shown below. Both the strain length, L0 and the shortening (L - L0) will be different when measured along a skewed line (red) and even longer along a line following the wall curvature (blue).  As both strain length and shortening increase when the curved line is used, the ratio will not be as affected,  but still, L0 will increase more than than the shortening.


The normalised annular displacement will be a measure of the global strain, making it less dependent on ventricular size (and thus, body size). Recent studies in children has shown normalised displacement to be an age independent measure of systolic performance (159, 214, 288), i.e. in the instance where the variation in LV size is greatest in the normals. The study in children (159) did show better correlation with EF over a wide range of pathology and age. In a small study in normal adults, it has shown better correlation with EF (217), which may be an indication that it removes variability due to LV size. However, introducing another measure (LV length) will increase the measurement variability of the composite parameter, and thus, the advantege is still unclear.

Thus, it is emerging evidence that normalisation of MAPSE, adds incremental value to the simple AV-plane motion. This is credible, some of the variability in MAE will be due to differences in LV size, and normalising will remove this variability and give a tighter relation to pumping parameters normalised for body size, and thus a higher diagnostic discriminatory value. This probably has most importance when normal variations in body and heart size is biggest (as in children) and least importance where normal variability is lower, and variation between normal and pathological is great (as in dilated heart failure). None of the methods for normalisation, however, have established superiority, and whether normalisation in adults gives better results, remains to be proven. (Firstly, because it increases measurement variability, secondly because the variability may increase due to the impact of foreshortening, and thirdly the differences in pathology may be greater than the differences in ventricular size in adults.

Global strain

Global strain and strain rate, may in theory be taken as global measures of ventricular function. It's, however, important to realise that different applications measures strain in different ways. It has been shown that strain measurements vary between vendors (373 - 383). 

This of course means that global strain has no meaning as a universal measure of LV function, only in relation to each manufacturer.

Global strain can be achieved simply by measuring and averaging the strain/strain rate in all segments of the ventricle.  However, there is one caveat:

Commercial software may give segmental values for six segments in each  imaging plane, resulting in a total of 18 segmental values. However, this results in equal weight given to all myocardial levels, despite there being much less myocardium in the apical level. In order to ensure that the average value gives similar weight to all parts of the myocardium, only four segments in the apical level should be included, as recommended by ASE/EAE (146). If not, the global measures may be misleading. (This is doubtful in the global strain measurement by 2D strain). The global strain by this application also is somewhat processing dependent.

Strain and strain rate, however should not be normalised for body size. Both measures are deformation per length, i.e. in fact normalised already for the size of the ventricle. Further normalisation for body size (which in fact is a correlate of healthy heart size), will then be erroneous. This is analogous to the fact that EF, which is stroke volume normalised to end diastolic volume, is never normalised again for BSA.

Global strain by speckle tracking has been introduced as a new measure of global left ventricular function (147). This compensates for the shortcomings of ejection fraction, being both more correct in the case of small or hypertrophic ventricles, and more sensitive (149). In the 2D strain application, it should be noted that the application relies heavily on the AV plane motion, and then distributes the motion along the wall. By this method, regional artifacts as drop outs and reverberations will have less impact, which is an advantage in measuring global function. (As it may be a disadvantage in regional function, as the same smoothing may reduce the sensitivity to regional reduced function).

It is unclear whether this application actually corrects for the reduced amount of myocardium in the apex, giving at the outset 6 segments per view, or 18 segments in total. Bull's eye plots seem to show 17 segments, but whether this is carried over to the calculation of global strain is uncertain.

Global longitudinal strain by this method, has shown a trend to be more sensitive to infarct size and correlate better with infarct mass than EF. Global longitudinal strain is thus a measure of wall shortening, normalised for the length of the wall, as length is measured along the curvature. Whether this allows sufficiently for the reduced amount of myocardium in the apex, seems unclear, as the referred study included 33 anterior and only 7 inferior infarcts. Annulus displacement had a slightly less diagnostic accuracy than global strain, but whether this was significant is less clear. Normalising the annular displacement for LV length (see below), did not show ovious improvement in diagnostic ability, in this group (150). However, annular displacement normalised for LV length IS a measure of longitudinal strain. Recent studies in children has shown normalised displacement to be an age independent measure of systolic performance (159, 214, 288), i.e. in the instance where the variation in LV size is greatest in the normals.

Thus, it is emerging evidence that global strain, adds incremental value to the simple AV-plane motion, at least in children. This is credible, some of the variability in MAPSE will be due to differences in LV size, and normalising will remove this variability and give a tighter relation to pumping parameters normalised for body size, and thus a higher diagnostic discriminatory value. This probably has most importance when normal variations in body and heart size is biggest (as in children) and least importance where normal variability is lower, and variation between normal and pathological is great (as in dilated heart failure). None of the methods for normalisation, however, have established superiority.


Normal systolic strain values

Normal values are necessary if measurements are to be used diagnostically. In addition, they will give additional information about physiology. In the north Tr÷ndelag population (HUNT) study, 1266 subjects without known heart disease, hypertension and diabetes were randomly selected from the total study population of 49 827, and subjects with clinically significant findings on echocardiography (a total of only 30) were excluded. (153) This is the largest normal population study of echocardiographic strain and strain rate rate to date. End systolic strain and peak systolic strain rate was measured by the combined tissue Doppler / speckle tracking segmental strain application of the Norwegian University of Science and Technology, but the results were compared to other methods in a subset of subjects, showing small differences. The study consisted of  673 women with a mean BP of 127/71 ,mean age of 47,3 years and BMI of 25.8 and 623 men, with mean BP of 133/77, mean age of 50.6 and BMI of 26.5. Both sexes were normally distributed with an SD of 13.6 and 13.7 years, respectively. 20% of both sexes were current smokers. Basic echo findings  are in accordance with other studies, like the findings of Schirmer et al (156, 157), so the study population may be assumed to be representative.


Normal values for global systolic left ventricular strain and strain rate by age and gender from the HUNT study. From (153).


Female
Male

End systolic strain (%)
Peak systolic strain rate
End systolic strain Peak systolic strain rate
< 40 years
-17.9% (2.1)
-1.09s-1 (0.12)
-16.8% (2.0)
-1.06s-1 (0.13)
40 - 60 years
-17.6% (2.1)
-1.06s-1 (0.13) -18.8% (2.2)
-1.01s-1 (0.12)
> 60 years
-15.9% (2.4)
-0.97s-1 (0.14) -15.5% (2.4)
-0.97s-1 (0.14)
Over all
-17.4% (2.3)
-1.05s-1 (0.13) -15.9% (2.3)
-1.01s-1 (0.13)
 
Values are given as mean ( SD). The customary definition of normal values as mean ▒ 2SD, giving about 95% of the normal population, results in wider normal limits than previously shown as cut off values in small patient studies. The values were normally distributed, and with no clinically significant differences between levels or walls. Values decline with age, as does the velocity.




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Editor: Asbj°rn St°ylen Contact address: asbjorn.stoylen@ntnu.no