xliii
Differentiating between diastolic and systolic dysfunction on clinical, radiographic and electrocardiographic findings is very difficult. More commonly the LV filling phase of diastole can be characterised by doppler echocardiography, radionuclide ventriculography, contrast ventriculography or magnetic resonance imaging (MRI) techniques108,109.
Although cardiac catheterization (CC) is considered to be the ‘gold standard’ for assessing LV filling pressure and “tau” which is an indicator of the rate of LV relaxation, CC is not essential to diagnosing diastolic dysfunction, and the use is further limited by its invasive nature, high cost and limited availability of hemodynamic studies110.
Pulsed-wave Doppler echocardiography which is a non- invasive method for an indirect measure of LV diastolic function is therefore the most practical and commonly used method for assessment of diastolic function. Its reliability, reproducibility, ease of performance and advances in applications over the past decades makes it the ideal tool for the assessment of diastolic function103.
Therefore a detailed and comprehensive diastolic study should include the measurement of transmitral and pulmonary venous flow velocities, and left atrial volume111.The pulse wave spectral tracings of transmitral flow usually demonstrates a biphasic waveform in the absence of atrial fibrillation, in which;
1. Peak flow velocity during rapid early diastolic filling (E),
2. Deceleration time (DT) from early peak velocity to extrapolation to baseline, 3. Peak velocity during late atrial contraction (A) and
4. Isovolumic relaxation time (IVRT) which is from closure of aortic valve to opening of mitral valve will be measured103.
xliv
Pulse wave spectral recordings of the pulmonary vein as it enters the left atrium is recorded, measurement of pulmonary venous waveforms include peak antegrade systolic (S) velocity, peak anterograde diastolic (D) velocity, the S/D ratio and the peak atrial reversal (Ar)velocity in late diastole. This traditional approach permits recognition of normal diastole as well as to classify the progression of diastolic dysfunction into three patterns: mild, moderate and severe filling patterns101.
Normal filling pattern
The determinants of LV filling, ventricular relaxation and effective chamber compliance change with increasing age, this leads to different diastolic filling patterns for different age groups. In normal young adult, the mean E/A, DT and IVRT are about 1.5, 166msec and67 msec respectively. Pulmonary venous inflow S/D ratio ≤ 1 and Ar of 0.19m/sec.
With aging, the rate of LV relaxation decreases with slower and less filling in early diastole and an increase contribution to LV filling by atrial contraction. Thus individual more than 65 years usually have means E/A ratio of <1, DT of about 200msec and IVRT of about 87msec.Pulmonary venous flow S/D < 1 and Ar <0.35m/sec35.
Mild diastolic dysfunction (Delayed relaxation)
This represent the stage of impaired LV relaxation with initially normal LA pressure (there is decrease transmitral gradient), leading to decrease early filling and increase filling with atrialcontraction112. This results in reverse E/A ratio (E/A< 1) that is abnormal for age, with prolonged
IVRT and DT, usually more than 100msec and 240msec respectively35. Moderate diastolic dysfunction (Pseudonormalization)
xlv
As diastolic dysfunction progresses, there are abnormalities in both LV relaxation andcompliance24.The LA pressure becomes elevated in order to maintain normal LV filling and cardiac output. This increased transmitral pressure gradient leads to increased early rapid filling with E/A ratio normalizing to > 1, shortening of DT and IVRT back to low normal values. This can be differentiated from normal filling on account of abnormal pulmonary venous S/D ratio forage113.
Severe diastolic dysfunction (Restrictive pattern)
As diastolic dysfunction (DD) progresses further, LV relaxation continues to be impaired with markedly reduced LV compliance and rising LV filling and LA pressures. This mimics the physiology of restrictive cardiomyopathy with the increased LA pressure causing LV pressure to quickly fall below LAP resulting in an early mitral valve opening and rapid early filling24. As early rapid filling occurs into the non-compliant LV, there is rapid equalization of LV and LA pressures leading to shortened DT. Also late atrial contraction into a non-compliant LV with high diastolic pressure leads to a reduced A velocity. Therefore E/A ratio is more than2, occasionally rising to 4 to 5 and pulmonary venous S/D ratio less than 135.
However, a modern comprehensive assessment of diastolic function should be performed not only by classifying the progression of diastolic dysfunction but by estimating the degree of LV filling pressure which is the true determinant of symptoms, signs and prognosis of heartfailure114.This is achieved by including the following maneuvers and/or ultrasound tools to the standard Doppler assessment of mitral inflow:
xlvi
1. Pulsed tissue Doppler imaging (TDI) of the mitral annulus: This allows non-invasive assessment of myocardial strain and has been shown to identify global and regional abnormalities in myocardial properties, with a high level of temporal resolution.
TDI differs from conventional doppler in that it utilizes a filter which eliminates high velocity and low amplitude signals reflected from blood cells, thereby allowing low velocity, high amplitude tissue signals to be analysed. Thus, TDI measures the early(e′) and late (a′) septal or lateral mitral annular diastolic velocity113.
2. Valsalva maneuver applied to the same mitral inflow pattern: This is performed by forceful expiration against a closed nose and mouth, resulting in increased in transthoracic pressure thus producing a complex hemodynamic process. In cardiac patients, a decrease of ≥ 50% in the E/A ratio is highly specific for increased LV filling pressures35.
3. Velocity flow propagation Vp: which is the slope of the first aliasing velocity during early filling, measured from the mitral valve to the apex by color M-mode. Normal Vp is ≥50 cm/s and correlates with the rate of myocardial relaxation115.
Table 1: Echocardiographic estimation of left ventricular filling pressure
Parameter Normal value Increased Left ventricular
Filling pressure ΔE/A ratio during valsalva
maneuver
<50% ≥50%
xlvii
ΔAr-A Duration (msec) <30 ≥30
E/Vp ratio <2.5 ≥2.5
E/ e′ratio <8 >8
LAVi (ml/m2) <34 ≥34
Δ = change
The pulmonary atrial reverse and transmitral atrial velocities duration difference (Ar- A)dur is relatively age-independent and values higher than 30m/s identify patients with elevated LV end-diastolic pressure with or without raised mean LAP, it also remains accurate in patients with normal EFs, mitral valve disease and hypertrophic cardiomyopathy35.
Velocity flow propagation Vp and tissue Doppler e′ are relatively load independent and characterize well LV relaxation, however, Vp and E/Vp ratio are limited in patients with LV concentric geometry, which can induce itself an increase of Vp and in those with normal LV volumes and ejection fraction (EF), who may present misleadingly normal Vp despite increased LV filling pressure115.
Valsalva maneuver applied to transmitral inflow and pulmonary venous flow have poor feasibility 60% and 80% respectively. E/e′ ratio can be performed in nearly 100% of the patients, it is also accurate in patients with sinus tachycardia and atrial fibrillation, thus has gained relevance in clinical practice35.
The detection of left atrial (LA) enlargement by 2-D echocardiographic estimation of LA volume can add further information in the intermediate gray range of E/e′ ratio between 9 and14, being an index of chronic increase of LV filling pressure, but cannot identify an acute
xlviii
increase of left ventricular filling pressure. LA volume also has a recognized prognosticvalue116.
Furthermore, it has been observed that a certain pattern of LV diastolic filling will result from multiple intrinsic factors such as LV relaxation (elastic recoil), LV compliance, left atrial pressure as well as patient’s conditions, such as load, age and heart rate. Thus, non-invasive Doppler measurements should be interpreted together with patient’s clinical condition inorder to provide an accurate assessment of LV relaxation and diastolic compliance.
Further information on diastolic dysfunction can be obtained by 2-D speckle tracking echocardiography, which quantify the multidirectional components of LV deformation (strain)either in systole or in diastole43,117. Figure 3 shows echocardiographic characteristics of left ventricular dysfunction
xlix
Echocardiograhpic classification of diastolic dysfunction
No rmal diasto lic functio n
Stage1 Imp aired relaxatio n
Stage11 P seudo no rmal
Stage111 Reversib le
restrictive
Stage1v Fixed restricted 1.0<E/A>2.0
DT160-240ms E/A <0.1
DT >240ms 1.0<E/A<2.0
DT 150-220ms E/A> 2.0
DT <150ms E/A> 2.0 DT <150ms 2.0
Velocity, m/s
E A
0.0
Time,ms Adur Time,ms Time,ms Time,ms Time,ms
Mitral Inflow at peak Valsalva
manoeuvre Mitral inflow
E/A<0.5
E A
2.0
0.0
Time. ms
E/A<0.5
Time. ms
E/A 0.5≥ E/A 0.5≥ E/A<0.5
Velocity, m/s
Time. ms Time. ms Time. ms
ARdur<Adur ARdur<Adur ARdur>Adur +30ms
ARdur>Adur +30ms
ARdur>Adur +30ms
Velocity, m/s
Pulmonary venous flow
2.0
S D
Ardur AR
Time, ms Time, ms Time. ms Time. ms
V <45msp V <45msp
Time. ms V <45msp
Time. ms Time. ms
Time. ms Time. ms
Time. ms Colour M-mode
propagation velocity
Doppler tissue imaging of mitral
annular motion
LV relaxation LV compliance Atrial pressure
Velocity, m/sDistance. cm 5.
0
0 0.15
E/Ea<10 E/Ea<10
Time, ms e’ a’
E/Ea>10
Time. ms
Time. ms
Time. sm Time. sm Time. sm Time. sm
Normal Normal
Normal Normal
Normal to
Impaired Impaired Impaired Impaired
V <45msp V <45msp
E/Ea>10 E/Ea>10 0.0
Figure 3 Echocardiographic classification of LV diastolic dysfunction. Reproduced and modified from Bonow et al. AHA/ACC Best Practice Guideline. Journal of the American College of Cardiology. 2006:48;(3)1-148118.
l