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Transcript
Medical Technology SA
Volume 25 No. 2 | December 2011
Peer reviewed ORIGINAL ARTICLE
A COMPARATIVE DOPPLER-CATHETERIZATION STUDY OF THE LEFT
VENTRICULAR END DIASTOLIC PRESSURE
JK Adam1 (PhD Clinical Tecnology) | K Shein2 (FCP (SA), Certificate in Cardiology) | J Chetty2 (BTech) | WNS Rmaih1 (MBChB, MSc
Pharmacology)
1
2
Durban University of Technology, Department of Biomedical and Clinical Technology, Durban, South Africa
Inkosi Albert Luthuli Central Hospital, Department of Cardiology, Durban, South Africa.
Corresponding author: WNS Rmaih | tel: +27 31 373 5291 | fax: +27 31 373 5295 | email: [email protected]
Abstract
Objectives To assess the correlation between the non-invasively measured ratio of early transmitral filling velocity to early diastolic
mitral annular velocity (E/E’) and invasively measured left ventricular end diastolic pressure (LVEDP) in our context.
Methods This is a prospective study of 66 patients (40 males and 26 females) who underwent elective coronary angiogram done
at Inkosi Albert Luthuli Central Hospital. Transthoracic spectral Doppler and tissue Doppler echocardiography was performed to
measure early diastolic transmitral flow velocities (E) and early diastolic medial and lateral mitral annular velocity (E’) respectively.
LVEDP was directly measured during left ventriculography in a cardiac catheterization laboratory. Statistical analysis was done to
compare E/E’ lateral and E/E’ medial to LVEDP in the study group and in different clinical subsets.
Results Among 21 patients with E/E’ lateral and 27 patients with E/E’ medial of >8, 17 (81%) lateral group and 18 (67%) medial
group had a LVEDP of >15mmHg, p value of 0.001 and 0.008 respectively. Raised E/E’ lateral ratio that is raised LVEDP was found
in 90.9% of females, 52% in those with diabetes and 41.9% in those with hypertension which is statistically significant but not in
smokers (30%) or those with dyslipidemia (31.3%) or a positive family history of premature coronary artery disease (20.5%).
Conclusion This study confirmed that non-invasively measured E/E’ ratio correlates well with LVEDP in our study population.
Keywords
Early transmitral filling velocity, early diastolic mitral annular velocity, invasively measured left ventricular end diastolic pressure
INTRODUCTION
non-invasive means to assess the LVEDP is sought.
Coronary artery disease (CAD) is the leading cause of cardiovascular mortality worldwide, with > 4.5 million deaths occurring
in the developing world, and despite a recent decline in developed countries, both CAD mortality and the prevalence of CAD
risk factors continue to rise rapidly in developing countries[1,2,3].
The evaluation and management of CAD in these countries
needs to be addressed.
Tissue Doppler Imaging (TDI) measures the velocity of myocardial motion using Doppler principles. While the usual Doppler
echocardiography measures the velocity of blood flow using the
Doppler signals from the fast moving blood cells, which are
of low amplitude, tissue Doppler measures low velocity, high
amplitude signals from the myocardial tissue motion[7].
The first changes of ischemia are metabolic and biochemical
leading to impaired ventricular relaxation and diastolic dysfunction, impaired systolic function and Electrocardiographic
(ECG) changes with ST segment changes, followed by increased
end diastolic pressure with left ventricular dyssynchrony, hypokinesis, akinesis and dyskinesis and lastly painful symptoms
of angina[4]. Myocardial perfusion imaging to detect metabolic
and biochemical changes is not always feasible in acute settings[5]. Therefore diastolic dysfunction is one of the earliest
manifestations that can be assessed for evidence of ischemia.
Raised diastolic filling pressure of the left ventricle is a measure
of left ventricular diastolic dysfunction[4]. Among the diastolic left ventricular filling pressure measurements, LVEDP is the
only measurement routinely done during left ventriculography.
LVEDP >16mmHg is one of the diagnostic criteria for LV diastolic dysfunction[6].
The role of assessing the LVEDP in the diagnosis of diastolic
dysfunction and the degree of the ischemic burden cannot be
over emphasized. Because of the invasively measured parameter, it cannot be done in routine clinical practice. Therefore a
Doppler echocardiography is widely used for the noninvasive
assessment of diastolic filling of the left ventricle (LV). Analysis
of the mitral inflow velocity curve has provided useful information for determination of filling pressures and prediction of prognosis in selected patients. However, mitral flow is dependent on
multiple interrelated factors, including the rate and extent of
ventricular relaxation, suction, atrial and ventricular compliance, mitral valve inertance, and left atrial pressure. These factors may have confounding effects on the mitral inflow; thus, it
has not been possible to determine diastolic function from the
mitral flow velocity curves in many subsets of patients[8].
To overcome these limitations of the mitral inflow parameters,
combinations of the mitral flow velocity curves with other Doppler parameters have been used. These include the pulmonary
venous velocity curves, color M-mode, and the response of
the mitral inflow to altered loading conditions. Tissue Doppler
imaging (TDI) of mitral annular motion has been proposed to
correct for the influence of myocardial relaxation on transmitral
flows. This has been shown to be an excellent predictor of diastolic filling in subsets of patients[8].
The ratio of early peak transmitral diastolic velocity (E), a measISSN 1011 5528 | www.smltsa.org.za
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Figure 1: Left ventricular end diastolic pressure
ure of the early diastolic filling, and late peak diastolic transmitral flow velocity (A), a measure of an atrial contraction (E/A) is
used to assess diastolic function. Under normal conditions, E is
greater than A and the E/A ratio is approximately 1.5[6]. In early
diastolic dysfunction, relaxation is impaired and, with vigorous
atrial contraction, the E/A ratio decreases to less than 1.0. As
the disease progresses, left ventricular compliance is reduced,
which increases left atrial pressure and, in turn, increases early
left ventricular filling despite impaired relaxation. This paradoxical normalization of the E/A ratio is called pseudonormalization. In patients with severe diastolic dysfunction, left ventricular filling occurs primarily in early diastole, creating an E/A
ratio greater than 2.0. The E- and A-wave velocities are affected
by blood volume, mitral valve anatomy, mitral valve function,
and atrial fibrillation, making standard echocardiography less
reliable[9]. In these cases, tissue Doppler imaging is useful for
measuring mitral annular motion.
The early diastolic velocity of the longitudinal motion of the
mitral annulus (E’) reflects the rate of myocardial relaxation[10].
In normal subjects E’ increases as transmitral gradient increases
with exertion or increased preload, whereas in patients with
impaired myocardial relaxation E’ is reduced at baseline and
does not increase as much as in normal subjects with increased
preload[10]. The E’ increases with increasing transmitral gradient
in healthy individuals, so that E/E’ is similar at rest and with
exercise (usually <8). Decreased E’ is one of the earliest markers
for diastolic dysfunction and is present in all stages of diastolic
dysfunction[10]. Because E’ velocity remains reduced and mitral
E velocity increases with higher filling pressure, the ratio between transmitral E velocity and mitral annular E’ velocity (E/E’),
correlates well with LV filling pressure, LVEDP[7].
This study is done to determine the application of these findings
in our context.
Volume 25 No. 2 | December 2011
Figure 2: Early diastolic mitral inflow (E) and early diastolic myocardial
annular velocity (E’)
A. On transthoracic apical four-chamber view the cursor is placed across the tips
of the mitral valve to obtain the early diastolic mitral inflow (E) and peak diastolic
myocardial velocity during atrial contraction (A).
B. On apical four chamber view the cursor is placed at the mitral annulus to obtain the
peak early diastolic mitral annular tissue velocity (E’), and peak late (atrial contraction)
diastolic myocardial tissue velocity (A’).
Figure 3: Lateral and medial tissue Doppler measurements
A. Transthoracic apical four-chamber view showing cursor placement for TDI
measurement of lateral myocardial tissue velocity (arrow).
B. Tissue Doppler myocardial velocities obtained at lateral mitral annulus: E’= peak
early diastolic myocardial tissue velocity, A’= peak late (atrial contraction) diastolic
myocardial tissue velocity, systolic = peak systolic myocardial tissue velocity.
C. Transthoracic apical four-chamber view showing cursor placement for TDI
measurement of medial myocardial tissue velocity (arrow).
D. Tissue Doppler myocardial velocities obtained at medial mitral annulus. E’= peak
early diastolic myocardial tissue velocity, A’= peak late (atrial contraction) diastolic
myocardial tissue velocity, systolic = peak systolic myocardial tissue velocity.
METHODS
to all prospective participants and informed consent in English
or Zulu was taken from all the participants. Ethical clearance
was obtained from the institutional ethical committee.
This is a prospective study of sixty six patients admitted at Inkosi
Albert Luthuli Central Hospital for elective coronary angiogram
during January 2008 to July 2008. Fourty (61%) males and 26
(39%) females. The ages range from 41 to 76 years with mean
age of 56+11 (mean age ± SD). An information sheet was given
Those with valvular heart disease, mechanical valvular prosthesis and patients with poor acoustic windows for transthoracic
imaging were excluded. The participants underwent full physical examination, electrocardiogram (resting and/or exercise),
chest X-ray, echocardiography or other non-invasive tests.
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Volume 25 No. 2 | December 2011
LVEDP was directly measured during left ventriculography using a pressure transducer in a cardiac catheterization laboratory
(Figure 1).
the invasively measured LVEDP. E/E’ lateral for males, females
and different clinical subsets of patients such as diabetes mellitus, hypertension, family history, smoking and hypercholesterolemia were also analyzed.
Non-invasive echocardiographic measurements
RESULTS
The Acuson Sequoia echocardiography machine was used for
the non-invasive measurements. With patients in the left lateral
decubitis position, transthoracic 2-D and Doppler echocardiography was performed.
Non-invasive E/E’ ratio vs. invasive LVEDP
Invasive catheterization measurements
In the apical four chamber view the pulse wave Doppler sample
gate was placed across the mitral valve at its tips and the early
transmitral filling velocity (E) was measured (Figure 2). Tissue
Doppler peak early diastolic velocities were acquired at the medial (septal) and lateral annular sites of the left ventricle from the
apical four chamber view (Figure 3). Thereafter the E/E’ ratios
were calculated.
SPSS version 16.0 (SPSS inc., Chicago, Illinois, USA) was used
to analyse the data. Bar graphs were used to display the variables. The student t test, Chi-Square test, Independent samples
test and cross tabulations was used to analyze the data. The
Chi-Square test was used in determining the p value. Statistical significance was defined as p < 0.05. The non-invasively
measured E/E’ medial and E/E’ lateral were then compared with
The study showed 81% of the patients in the E/E’ lateral group
had a p < 0.001 and 66.7% of the patients in the E/E’ medial
group had a p < 0.008 (Figure 4 & 5). The sensitivity and specificity for the non-invasively measured E/E’ lateral was 55% and
81% and for E/E’ medial was 58% and 74% respectively with
positive predictive value of 81% for E/E’ lateral and 67% for
E/E’ medial. Lateral E/E’ was significantly higher in patients with
LVEDP ≥ 15 mmHg. The correlation of the LVEDP with lateral
annulus was equivalent or better than the medial annulus.
Non-invasive E/E’ ratio vs. invasive LVEDP with regards to
gender
The E/E’ lateral which correlates with high LVEDP were found
in 90.1% of females and 70% of males (Figure 6). The E/E’ medial which correlates with high LVEDP was found in 75% of
females and 60% of males. The sensitivity and specificity for the
noninvasively measured E/E’ lateral in females was 67% and
Figure 4: Non-invasive E/E’ lateral ratio vs. Invasive LVEDP.
Figure 5: Non-invasive E/E’ medial ratio vs. Invasive LVEDP.
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Figure 6: Non-invasive E/E’ lateral ratio vs. invasive LVEDP with regards to gender.
Figure 7: The correlation between diabetes mellitus (DM) and E/E’ lateral.
Figure 8: The correlation between hypertension (Hpt) and E/E’ lateral.
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Volume 25 No. 2 | December 2011
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91% and for E/E’ medial was 60% and 73% respectively with
positive predictive value of 91% for E/E’ lateral and 75% for
E/E’ medial. The sensitivity and specificity for the non-invasively
measured E/E’ lateral in males was 44% and 88% and for E/E’
medial was 56% and 75% respectively with positive predictive
value of 70% for E/E’ lateral and 60% for E/E’ medial.
Non-invasive E/E’ ratio vs. invasive LVEDP with regards to
anthropometric and clinical profiles
Age, height, weight and body mass index (BMI) was not found
to be associated with high LVEDP.
Study 52% (13/21) of patients with DM and 41.9% (18/21) with
Hypertension had a high E/E’ lateral ratio and high LVEDP which
is statistically significant (Figure 7 & 8). Positive family history
of premature coronary artery disease (20.5%), dyslipidemia
(31.3%) and smokers (30%) were not found to be associated
with high E/E’ ratio and LVEDP (Figure 9 & 10).
DISCUSSION
There is a correlation between the non-invasively measured E/E’
and the invasively measured LVEDP. High LVEDP was found
in 81% of the patients in the E/E’ lateral > 8 group and 66.7%
of the patients in the E/E’ medial >8 group. This is considered
statistically significant for this population. European society of
cardiology concensus statement, 2007[6], recommended that
E/E’ ≤ 8 suggests normal filling pressure, > 15 is abnormal filling
Volume 25 No. 2 | December 2011
pressure. Nagueh[8] et al also showed E/E’ lateral > 10 correlated with raised left ventricular (LV) filling pressures (LVEDP).
Although a small sample size was used over a selected study
period, the findings of this study indicate a trend that is comparable to other similar studies. This study also showed diastolic
dysfunction and raised LVEDP more common in females than
in males. Age, height, weight and body mass index (BMI) was
not found to be associated with high LVEDP. Other studies have
shown that the older age group (≥60 years)[11] and obesity are
associated with a high LVEDP but not in this study. This can be
explained by the younger age group in this study with a mean
age of 56 ± 11 and exclusion of patients with poor acoustic
windows who may be obese.
It is well known and also identified in this study that diabetes
mellitus (DM), hypertension (Hpt) and females are associated
with diastolic dysfunction, that is raised LVEDP. Patients with
traditional risk factors and higher LVEDP are at a greater risk
for adverse cardiovascular outcome[1]. Therefore non-invasive
tissue Doppler measurement of E/E’ can be used to risk stratify.
Clinical risk factors such as family history, dyslipidemia and
smoking were not found to be associated with high LVEDP.
Therefore high LVEDP in these patients are possibly due to
ischemia. Occlusive coronary artery disease was confirmed in
53 patients, while 13 patients had non-occlusive normal coronary arteries.
Figure 9: The correlation between dyslipidemia (dyslipid) and E/E’ lateral.
Figure 10: The correlation between non-smokers, current smokers, ex-smokers (Ex) and E/E’ lateral.
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Volume 25 No. 2 | December 2011
LIMITATIONS
CONCLUSIONS
The number of cases selected in this study was small and limited to patients with coronary artery disease (53/66), especially
in the Indian community. Therefore it cannot be extrapolated to
other population groups and other clinical subsets such as valvular heart disease. Although E/E’ ratio can be easily measured,
it is not easily performed on those with poor acoustic window
such as patients who are obese, have crowded ribs, scars on the
anterior chest wall and those with chronic obstructive airway
disease. Tissue Doppler also requires proper alignment of the
sample gate. The influence of regional wall motion abnormality
on the mitral annulus movement is still unknown, therefore we
cannot exclude that it could have affected E/E’ ratio.
The trend /observations developed in this study suggests that
non-invasively measured E/E’ ratio correlates well with high
LVEDP in our study population. Therefore it may be used to estimate the LVEDP in routine clinical practice, which in turn provides information regarding diastolic function and severity of
CAD. E/E’ lateral > 8 correlates with raised LVEDP > 15mmHg
was found in females (90.9%), those with diabetes (52%) or
hypertension (41.9%)but not in smokers (30%), those with
dyslipdemia (31.3%) or family history of premature coronary
disease (20.5%).
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Further larger studies are needed to confirm our finding in different racial groups and clinical subsets.