Nghiên cứu đặc điểm các thông số lượng giá áp lực đổ đầy thất trái trên siêu âm tim ở bệnh nhân suy tim độ III IV tt tiếng anh

1

MINISTRY OF EDUCATION AND

MINISTRY OF

TRAINING

DEFENCE

MILITARY MEDICINE ACADEMY
======

LÊ THỊ BÍCH VÂN

STUDY THE CHARACTERISTICS OF SEVERAL PARAMETERS
USED TO ESTIMATE THE LEFT VENTRICULAR FILLING
PRESSURE ON DOPPLER ECHOCARDIOGRAPHY IN NYHA III
– IV
HEART FAILURE PATIENT
Specialized: Internal medicine
Code: 9720107
SUMMARY OF MEDICAL DOCTORAL THESIS

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HA NOI - 2019

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THE RESEARCH WORK ACCOMPLISHED AT
MILITARY MEDICAL UNIVERSITY
Scientific supervisors:
1. Phạm Nguyễn Vinh MD, PhD

Critic 1: Phạm Hữu Văn, MD, PhD
Critic 2: Phạm Nguyên Sơn, MD, PhD
Critic 3: Hoàng Đình Anh, MD, PhD
The Thesis will be defended against the Jury of
Military Medical University on: … hour, .. month,
date

This Thesis can be referred at:
1
2

National Library of Viet Nam
Library of Military Medical University

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INTRODUCTION
Heart failure (HF), the terminal stage of almost every known
cardiac disorders, is one of the most frequently encountered medical
conditions in the clinics and its prevalence has been shown to

increase recently. In Vietnam, the incidence of heart failure also has
an escalating tendency and a major problem that cardiologists usually
face is that serious HF has a high mortality rate.
Advanced HF patients having reduced left ventricular systolic
function usually have significant concomitant systolic and diastolic
function disorders leading to an increase in left ventricular filling
pressure (LVFP). In the clinical context, the LVFP has important
diagnostic, prognostic values which help cardiologists choose the
right management timely. LVFP is considered to be: end-diastolic
ventricular pressure, mean pulmonary capillary wedge pressure. In
addition

to

cardiac

catheterization

which

allows

accurate

measurement of the end-diastolic ventricular pressure, the pulmonary
capillary wedge pressure, etc., Doppler ultrasound has long been
recognized as a reliable imaging modality that can be used to
evaluate increased LVFP clinically. In our country, several studies on
evaluating diastolic function using Doppler ultrasound were
conducted on a variety of patient populations. Some studies strived to

find a relationship between Doppler ultrasound parameters and LVFP,
and however they were done in a discrete way and therefore has a
limited specificity and sensitivity. In 2016, according to the ASE’s
guidelines, LVFP measurements in HF patients with reduced EF need

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an integration of Doppler parameters and tissue Doppler has become
very valuable and beneficial in the clinical context. On the other
hand, the invasiveness of cardiac catheterization is considered to be
more difficult, expensive and riskier than Doppler echocardiography
and is rarely used in real-life HF patients; in addition, measuring
LVFP based on symptoms such as dyspnea, neck vein distension,
chest films, etc. has certain limitations and highly depends on clinical
examination skills. LVFP is considered as elevated when enddiastolic left ventricular pressure > 16 mmHg or PCWP > 12 mmHg,
which is in accordance with the changes in Doppler parameters,
including: peak E-wave velocity, E/A ratio, E/e’ ratio, tricuspid
regurgitation peak velocity (TRV), left atrial volume index (LAVi)
that were published in LVFP measurements guidelines of ASE 2016
and there are not yet study in Vietnam. Therefore, we decide to
conduct this this thesis: “ Study the characteristics of several
parameters used to estimate the left ventricular filling pressure on
Doppler echocardiography in NYHA III – IV heart failure patient”
1. This study with the following objectives in mind:

a.

Evaluating the characteristics of several parameters used to

estimate the LVFP on Doppler echocardiography and tissue
Doppler including: peak E-wave velocity, E/A ratio, E/e’
ratio, peak TRV, atrial volume index in NYHA III-IV HF
patients with EF equal to 40% or less

b.

Identifying the relationship between several parameters used
to measure LVFP and various clinical, sub-clinical

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characteristics in NYHA III-IV HF patients with EF equal to
40% or less.
2. Scientific significance, practice and make new contributions to
the topic
This study has scientific significance, practice and make new
contributions to Cardiology, especially Echocardiology, such as :

•

The study found that the difference of the characteristics of
several parameters used to estimate the LVFP on Doppler
echocardiography and tissue Doppler including between
patients with advanced heart failure and control group.

•

The integration of these 5 parameters used to
estimate LVFP according to ASE 2016 in our
study demonstrates that there is no statistical
significance

in

incidence

of

elevated

LVFP

between the EF< 30% group and 30 < EF ≤
40%, between NYHA III and NYHA IV patients,
between the Ischemic heart disase and BCTTG,
between Male-Female and age group.

•

There are 83 patients (82,2%) identified to have elevated
LVFP, the rest identified to have normal LVFP.

•

The E/e’ ratio > 14 when used alone to estimate elevated
LVFP (41.6%) will miss half of the time where there is an
elevated LVFP compared to the case where 5 parameters

were integrated and used (82,2%).

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•

Based on peak E-wave ratio and E/A ratio from the
transmitral flow, it is confirmed that 8.91% of the cases don’t
have elevated LVFP and 44,55% have elevated LVFP without
the need to investigate other parameters, however, almost
half of the cases need more parameters to confirm the
existence of elevated LVFP.

•

The study shown that some relationships between several
parameters used to measure LVFP and various clinical, subclinical characteristics in NYHA III-IV HF patients with EF
equal to 40% or less.

3. The layout of thesis
+ The thesis has 143 pages include sections: questioning (2
pages), Chapter 1: Overview (page 43), Chapter 2: Objects and
methods of research (21 pages), Chapter 3: The results research (46
pages), chapter 4: Discussion (30 pages). Conclusion (2 pages).
Recommendations (1 page).
+ The thesis has 48 tables, 17 charts, 13 pictures, 01 diagrams.
The thesis uses 125 reference documents (17 Vietnamese, 56
English).

CHAPTER 1
OVERVIEW OF DOCUMENTS
1.1. General and epidemiological chronic heart failure with
reduced ejection fraction
There are many changes in the definition of HF. In 1950s, HF is a
condition in which the dysfunction of myocardial contraction causes

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heart to lose its ability to supply blood to the body appropriately. This
condition first occurs when the patient exerts, and then it happens
even when the patient rests.In 2016 - 2017, the definition based on
ASC and ESC :
HF is a clinical syndrome characterized by typical symptoms (e.g.
breathlessness, ankle swelling and fatigue) that may be accompanied
by signs (e.g. elevated jugular venous pressure, pulmonary crackles
and peripheral oedema) caused by a structural and/or functional
cardiac abnormality, resulting in a reduced cardiac output and/ or
elevated intracardiac pressures at rest or during stress.
From 2016 up to now, ESC offers some of new definitions :
The main terminology used to describe HF is historical and is based
on measurement of the LVEF.
- HF with normal LVEF (HFpEF) : LVEF ≥ 50%,
accompanied with signs and/or symptoms, elevated
natriuretic peptide level or at least abnormal structure
of heart (left ventricular thickness and/or dilated left
atrium) or left ventricular diastolic dysfunction.
- HF with mild reduced EF (HFmrEF)] : LVEF in the range of 40 –

49%, accompanied with signs and/or symptoms, elevated natriuretic
peptide level or at least abnormal structure of heart (left ventricular
thickness and/or dilated left atrium) or left ventricular diastolic
dysfunction.
- HF with reduced EF (HFpEF)] : LVEF typically considered equal or
less than 40% accompanied with signs and/or symptoms.
Epidemiology

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It is estimated that 38 million people worldwide have heart failure
(HF), with most published studies reporting a prevalence of between
1% and 2% of the adult population. Data from Europe and North
America suggest that 1%–2% of all hospital admissions are related to
HF, amounting to more than 1 million admissions annually, with 80–
90% being due to decompensation of chronic HF. The syndrome still
carries a poor prognosis: 5% to 10% of patients die during hospitalization, with a further 15% dying by 3 months, and over half of
patients die within 5 years of their first HF hospitalization. Rates of
rehospi- talization are also high. The financial burden of HF,
principally due to the cost of hospitalization, is expected to increase
substantially in the coming decades due to the aging of the population
worldwide.
1.2. Left ventricular filling pressure
The term LV filling pressures can refer to mean pulmonary capillary
wedge pressure (PCWP) (which is an indirect estimate of LV
diastolic pressures), mean left atrial pressure (LAP), LV pre-A wave
pressure, mean LV diastolic pressure, and LV end-diastolic pressure
(LVEDP).

The optimal performance of the left ventricle depends on its ability to
cycle between two states: (1) a compliant chamber in diastole that
allows the left ventricle to fill from low LA pressure and (2) a stiff
chamber (rapidly rising pressure) in systole that ejects the stroke
volume at arterial pressures.
The ventricle has two alternating functions: systolic ejection and
diastolic filling. Furthermore, the stroke volume must increase in

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response to demand, such as exercise, without much increase in LA
pressure. The theoretically optimal LV pressure curve is rectangular,
with an instantaneous rise to peak and an instantaneous fall to low
diastolic pressures, which allows for the maximum time for LV
filling. This theoretically optimal situation is approached by the
cyclic interaction of myofilaments and assumes competent mitral and
aortic valves. Diastole starts at aortic valve closure and includes LV
pressure fall, rapid filling, diastasis (at slower heart rates), and atrial
contraction.
Elevated filling pressures are the main physiologic consequence of
diastolic dysfunction. Filling pressures are considered elevated when
the mean pulmonary capillary wedge pressure (PCWP) is > 12 mm
Hg or when the LVEDP is > 16mm Hg.
1.2.4 Estimation of the left ventricular filling pressure by Doppler
echocardiography
Chart 2.1 shows the estimation of the left ventricular filling pressure
by Doppler echocardiography in HF patients who has reduced LVEF
(classified by ASE 2016).

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Chart 2.1: Algorithm for estimation of LV filling pressures and
grading LV diastolic function in patients with depressed LVEFs and
patients

with

myocardial

disease

and

normal

LVEF

after

consideration of clinical and other 2D data.
1.3. Summary some research on the characteristics of parameters
used to estimate the LVFP by Doppler echocardiography in
patients with advanced heart failure
In the prospective study of Sherif F. Nagueh et al., 79 consecutive
patients with decompensated heart failure had simultaneous

assessment of left ventricular and right ventricular hemodynamics
invasively and by Doppler echocardiography. They measured some
parameters such as E, A, E/A, DT, IVRT, mean value of E/e',
pulmonary artery systolic pressure, LAVi, etc. This study
demonstrated that Doppler echocardiography is a reliable assessment

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of right and left ventricular hemodynamics in patients with acute
decompensated heart failure.
In the single-center clinical trial of Luis E.Rohde et al., they included
96 outpatients whose LVEF = 26% ± 6%. The patients were
diagnosed HF about 6 months or so regardless of cause, previous HF
admission within 3 months. They compared an echocardiographyguided strategy aimed at achieving a near-normal hemodynamic
profile and a conventional clinically oriented strategy for HF
management. The outcome is that the hemodynamically oriented
echocardiography-based strategy (using standard parameters of ASE)
is an easy and safe approach and it reduces incidence of HF.
In an prospective study, Bruno Pinamonti et al. examined 110
patients with dilated cardiomyopathy (DCM), LVEF <50%. When
assessed transmitral flow velocity curve (E, A, E'A, EDT), they found
that Doppler ultrasound used to evaluate the improvement of LV
filling pressure in the corrected medical treatment period helps
clinicians to prognose and to classify patients to monitor closely or
heart transplantation.
In Vietnam, there are few studies about the characteristics of
parameters of Doppler ultrasound performing in HF patients with
reduced LVEF, such as Nguyen Duy Toan et al., Nguyen Tien Binh et

al., Quyen Dang Tuyen et al., Nguyen Oanh Oanh et al. There is no
research about the combination of these parameters to estimate LV
filling pressure.
Nguyen Thu Hoai et al. evaluated 52 first myocardial
infarction

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patients.

They

performed

Doppler


13
echocardiography in patient within 24 hours after MI
occurred and recorded left ventricular end diastolic
pressure from cardiac catheterization. The results
showed that 11 patients (21.2%) had left ventricular
end diastolic pressure in normal range (≤12 mmHg),
41 patients (78.8%) had elevated left ventricular end
diastolic

pressure.

Left

atrial

volume

index

was

extremely correlated with left ventricular end diastolic
pressure (r = 0,78) and also E/e' ratio. Left atrial
volume index was moderately correlated with the
parameters of LV systolic function, such as E/A ratio (r
= 0,63), EDT (r = -0,43), IVRT (r = -0,52), A-Ar
(r=0,61). There is moderate correlation between left
atrial volume index with pulmonary artery systolic
pressure (r = 0,67).

CHAPTER 2
SUBJECTS AND METHODS RESEARCH
2.1. Research subjects
We enrolled 167 patients in The HCMC Heart Institute and Columbia
Asia Bình Dương Hospital from April 2016 to June 2018.
2.1.1. Diseases group

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101 inpatients with NYHA classes III-IV and LVEF ≤
40% at The HCMC Heart Institute.

Selection criteria:

-

HF

patients

with

reduced

LVEF

(classified

by

recommendation of ESC 2016)

-

HF classification of NYHA

-

The major HF causes are ischemic heart disease and dilated
cardiomyopathy.

Exclusion criteria:

-

HF patients with cardiac arrhythmia : atrial fibrillation, block
A-V high grade.

-

HF patients who have pacemaker

-

HF patients using ventilator or having severe pulmonary
disease (severe COPD, severe asthma, etc), calcified mitral
valve.

-

HF patients with valve stenosis or mechanical valve.

-

Patients with HF caused by congenital heart disease or
rheumatoid heart disease.

-

Hypertrophic cardiomyopathy or restrictive cardiomyopathy

-

Pulmonary artery hypertension not caused by heart disease

-

Patients refuse participating in the research

-

Echocardiographic images are unclear.

2.1.2. Control group

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66 healthy people who do not have any cardiovascular disease visit
Columbia Asia Bình Dương Hospital for health examination.
Selection criteria:

-

No history of cardiovascular disease

-

No risk of HF such as hypertension, coronary disease,
diabetes.

-

Normal clinical examination, no sign or symptom suggesting
HF (based on criteria of ESC 2016)

-

Agree to participate in the research.

Exclusion criteria:

-

Ultrasound

image

myocardiopathy

has

evidence

(hypertrophy,

of

valve

myocardial

stenosis,

infiltration),

calcification of valve

-

Echocardiographic images are unclear.

-

Patients refuse participating in the research

2.2. Method of study
2.2.1. Study design: descriptive, cross-sectional, controlled study.
2.2.2. Sampling studies
Applying the formula for calculating the sample size in the study
described

t = 1.96

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= 0.9
We use standard deviation of mean value of E/A ratio from the study
of Jaroslav Meluzin et al. in 2011 [51].

e (absolute error) = 0.18
Based on this formula, we will have 97 people participating in the
research.
In our study, we included 101 patients who met the selection criteria.
2.2.3. Location and time studies

-

Research at The HCMC Heart Institute and Columbia Asia
Bình Dương Hospital

-

Research period : from April 2016 to June 2018

2.2.4. Materials research

-

Philips HD XE Revision Ultrasound Machine with 2-4-MHz
transducer.

-

We perform general ultrasound and Doppler ultrasound,
tissue Doppler to record the parameters used to estimate LV
filling pressure (based on guidelines of ASE 2016). This
procedure is done by researchers themselves (Chart 2.1)

2.2.5. Analysis and data management

After collecting data, we check the completeness and reasonability of
data and correct bias. Then data will be recorded by Epidata 3.1 and
analyzed by Stata 14.2.
We describe qualitative variables such as sex, causes and risks of HF
by ratio and percentage. The quantitative variables such as LVEF,
E/A ratio, pulmonary artery systolic pressure which has normal

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distribution will be described by mean, SD. The quantitative
variables which has abnormal distribution will be described by
median and quartile.
We use t-test when comparing mean values of variables that has
normal distribution, Mann-Whitney U test for variables that has
abnormal distribution, ANOVA test for comparing mean values of
variables from different groups which have normal distribution and
Kruskal-Wallis for variables from different groups which have
abnormal distribution.
We use χ2 test to compare percentage of two groups or percentage of
studied group and the theoretical ratio. Fisher Exact is used when at
least one value of 2xn tables has expected value less than 1 or 20%
expected values equal or less than 5.
P-value 0.05 means this is statistical significance.
Data is presented by tables and charts.
2.4. Ethics of the research
Our research is reviewed by The Ethical Committee of The HCMC
Heart Institute and The Ethical Committee of Columbia Asia Bình
Dương Hospital. Also, the directors of these hospital give us

permission to collect data from their patients.
Data will be kept in secret carefully and used for study purpose.
The results are used to improve the quality of health care and
treatment.

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CHAPTER 3
RESEARCH RESULTS
3.1. General Characteristics of the study population
Age : the average age of our study population is 62 ± 15 age, the age
of severe HF patients is ranged from 60 to 79 age.
Sex : male is 1.88 times higher than female. Sex ratios of disease
group and control group are equal. The average age of disease group
is 1.8 times higher than one of control group. Because of the
significant difference of age between two group, we only use the
parameters of the control group for reference.
Table 3.2. The subgroup in our study
Subgroup
Patient, n (%)
Group with 30% < EF ≤
38 (37,62)
40%

Group with EF ≤ 30%
63 (62,38)
Group with NYHA III
43 (42,57)
Group with NYHA IV
58 (57,43)
Group with dilated
36 (35,64)
myocardiopathy
Group with ischemia heart
65 (64,36)
disease
Group aged 20 – 39
8 (7.92)
Group aged 40 – 59
32 (31,68)
Group aged ≥ 60
61 (60,40)
Group with QRS ≥ 120 ms
30 (29,70)
Group with QRS < 120 ms
71 (70,30)
Disease group : 101 inpatients with NYHA classes III-IV
and LVEF ≤ 40%, after analysing, we divided this group
to subgroup listed (table 3.2).

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3.2. Characteristics of Doppler echocardiographic parameters
3.2.1. Characteristics of several Doppler echocardiographic
parameters of study population :
Table 3.13. Study population’s characteristics of the spectral
Doppler through mitral valve and tissue Doppler
Characteristics

Disease group
n =101

Control
group
n =66

P

E (cm/s) ( ±SD)

86,68± 27,19

85,19± 13,53

>0,05

E/A ( ±SD)

1,99± 1,18

1,63± 0,41

0,006

EDT (ms) ( ±SD)

142,68±71,51

208,57±46,35

<0,001

E/e’tb ( ±SD)

14,22±5,85

6,40±1,04

<0,001

E/e’tb > 14, n (%)

42 (41,58)

0

E/e’tb ≤ 14, n (%)

59 (58,42)

66 (100)

e' vách ( ±SD)

5,14±1,72

12,03±2,25

<0,001

e' bên ( ±SD)

8,16±3,75

15,02±2,93

<0,001

E/e' vách ( ±SD)

18,15±7,08

7,24±1,31

<0,001

E/e' bên ( ±SD)

12,50±6,32

5,81±1,07

<0,001

<0,001

E/A ratio of disease group is significant higher than that of
control group. The mean EDT of disease group is significant lower
than that of control group. There is a statistical correlation between
HF status with E/A ratio and EDT (p<0.05). The mean of E/e', septal
E/e' and lateral E/e' in disease group is significant higher than those
of control group (p<0.001). Contrastly, septal e’ and lateral e’ values

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in disease group is significant lower than those of control group
(p<0.001). Mean E/e’ ratio that is more than 14 is observed in the
disease group (42%), not in the control group.
Table 3.14. The peak velocity of flow at tricuspid valve,
pulmonary artery pressure and left atrial index in the study
population
Characteristics

Disease group
n =101

Control
group
n =66

P-value

TRV > 2,8 m/s, n (%)

63 (62,38)

0

TRV ≤ 2,8 m/s, n (%)

38 (37,62)

66 (100)

Pulmonary artery systolic
pressure (mmHg) ( ±SD)

36,03± 11,75

19,83± 3,19

<0,001

TRV (m/s) ( ±SD)

2,96 ± 0,49

2,22± 0,18

<0,001

LAVi > 34 ml/m2, n (%)

84 (83,17)

34 (51,52)

LAVi ≤ 34 ml/m2, n (%)

17 (16,83)

32 (48,48)

Mean LAVi (mL/m2)

55,82±29,13

36,05±12,04

46,37±10,87

34,23±4,79

<0,001

<0,001

( ±SD)
LAd (mm) ( ±SD)

<0,001
<0,001

The peak velocity of flow at tricuspid valve TRV > 2.8 m/s is
observed in disease group (62%), not in control group. The value of
pulmonary artery systolic pressure in disease group is statistically

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higher than in control group (36.0±11.8 vs 19.8±3.2 mmHg). The left
atrial index (LAVi>34ml/m2), mean left atrial index and left atrial
diameter in disease group is significantly higher than in control
group.
3.2.2. Estimating LV filling pressure based on ASE guideline 2016
Estimating LV filling pressure by incorporating many parameters
based on ASE guideline 2016, we divided the study population into
two groups :

-

Group with clearly elevated LV filling pressure on ultrasound
: 83 patients (82.18%)

-

Group with non-elevated LV filling pressure on ultrasound :
18 patients (17.82%)

In the disease group, 17.8% patients have LV diastolic dysfunction
grade I, 37.6% patients have LV diastolic dysfunction grade II, and
44.6% patients have LV diastolic dysfunction grade III.
In the elevated-LV-filling-pressure group, 54.2% patients have LV
diastolic dysfunction grade III.

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Chart 3.3. The results of estimating LV filling pressure based on
ASE 2016
3.3.1. The relationship between LV filling pressure and some
clinical and subclinical characteristics
With clinical characteristics : there is no statistical relationship

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between LV filling pressure and these characteristics such as age, sex,
heart rate, systolic and diastolic blood pressure (p>0.05)
With subclinical characteristics : we can observe that the restrictive
spectral in patients with elevated LV filling pressure is 7 times higher
than in patients with non-elevated LV filling pressure. Mean T/LN
ratio in patients with elevated LV filling pressure is significant higher
than in patients with non-elevated LV filling pressure. The number
patients with elevated LV filling pressure who have severe mitral
valvular regurgitation (grade 2/4) is 1.8 times higher than the number

of patients with non-elevated LV filling pressure.
Contemporarily, when analyzing multiple factors which may cause
elevated LV filling pressure, we noted that there is only a relationship
between LV filling pressure and restrictive spectral Doppler (p<0.05).
The patients who have restrictive spectral Doppler have 29.8 times
risk of elevated LV filling pressure higher than the patients who do
not have restrictive spectral Doppler (OR=29,8; CI 95%: 3,4-261,8).
CHAPTER 4
DISCUSSION
4.2. Characteristics of several Doppler echocardiographic
parameters :
4.2.1. The spectral Doppler through mitral valve
The LV filling pattern and the spectral Doppler through mitral valve
change in the HF patients. In the early stage of HF, the quantity and
rate of filling decrease and those have close relationship with filling
pattern in atrial contraction time, it is also the slow ventricular
relaxation time. Later, the early filling rate becomes normal. This is

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just “artificial normal” which is affected by the increase of left atrium
pressure. Moreover, in the later phase of HF, the peak of early filling
rate may be higher than normal.
In our study, the result E/A >1.5 is matching with outcome of many
other researches such as Nguyen Duy Toan, Dokinish, Hansen,
Giannuzzi, Rihal, Pinamonti, however, that is higher than the
outcome of Ritzema, perhaps because the sample size of Ritzema’s
study is extremely small, just 15 patients.

4.2.2. E/e’ ratio and e’ value in tissue Doppler
The result mean E/e’ >14 is one of basic non-invasive parameters
used to describe elevated LV filling pressure. When predicting if LV
filling pressure is increased or not and when making a prognosis, this
ratio is more valuable than the other simple tissue Doppler
parameters such as e’ value or the other standard parameters used to
evaluate LV filling pressure, even with the spectral of pulmonary
vein.
In our study, mean E/e’ ratio (14,22±5,85) is lower than the research
of Dokainish. Furthermore, septal E/e’ and lateral E/e’ of our finding
are lower than those of Ritzema’s study.
4.2.3. Peak tricuspid regurgitant velocity
Left heart disease is the most common cause of pulmonary artery
hypertension, because of the response with elevated LV/LA filling
pressure from various heart disease. Pulmonary artery pressure can
increase in HF patients who will have worse symptoms and
prognosis.
In our research, we performed TRV with all patients (100%). We

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