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International Journal of Pharmaceutical Research | Oct - Dec 2020 | Vol 12 | Issue 4
Research Article
Differential diagnostic criteria for dilatational
cardiomyopathy and nonreumatic myocarditis in
children
DILOROM AKHMEDOVA
1
*, DILFUZA RUZMATOVA
2
, NIGORA ALIEVA
3
, SAYYORA AKHMEDOVA
4
1
Tashkent Pediatric Medical Institute Republic of Uzbekistan
2,4
Republican Specialized Scientific and Practical Medical Center of Pediatrics of the Ministry of Health
of the Republic of Uzbekistan
3
Tashkent Pediatric Medical Institute Republic of Uzbekistan
*Corresponding Author
Email ID: diloromahmedova@mail.ru, dilfuzaruzmatova87@mail.ru, diloromahmedova@mail.ru,
drsayyora@gmail.com
Received: 16.04.20, Revised: 16.05.20, Accepted: 16.06.20
ABSTRACT
Dilatational cardiomyopathy is a severe pathology in childhood, which requires careful study of clinical data and
data from functional diagnostics methods (ECG, ECHO) at early stages of detection. This scientific study aimed
to determine the clinical, functional features of dilated cardiomyopathy and nonreumatic myocarditis in
children. We examined 60 children with DCMP and 40 children with non-reumatic myocarditis aged from 2
months to 18 years, hospitalized in the cardioreumatology department of the Republican Specialized Scientific-
Practical Medical Center for Pediatrics of the Ministry of Health of the Republic of Uzbekistan. The control
group consisted of 30 practically healthy children.
Keywords
: children, cardiomyopathy, echocardiography, radiography, electrocardiography.
INTRODUCTION
According to modern concepts, dilatational
cardiomyopathy (DCMP) is defined as a disease
of the cardiac muscle of unknown or obscure
etiology, characterized by cardiomegaly due to
dilatation of heart cavities, especially of the left
ventricle (LV), progressive reduction of myocardial
contractility, suddenly developing and progressive
heart failure, arrhythmic and thromboembolic
syndrome, which often ends in sudden death [1].
Dilatation cardiomyopathy is characterized by a
continuously progressing course, holds a leading
position in the structure of disability and mortality
in children, is the main cause of chronic heart
failure in childhood [2]. The prevalence of dilated
cardiomyopathy varies from 40 cases per
100,000 per year in Europe. It is more common
in boys than in girls. The proportion of dilated
cardiomyopathy, among other cardiomyopathies,
is 60% (8). The rate of sudden death among
children with dilated cardiomyopathy ranges from
1.5% to 4%, arrhythmia being the cause of death
in most cases. Cardiac rhythm disorders are both
bradycardic
(atrioventricular
block)
and
tachycardic (unstable ventricular tachycardia). The
risk factors for sudden death include polymorphic
ventricular extrasystoles. However, heart rhythm
disorders are not an independent risk factor for
sudden death, as they are closely associated with
left ventricular dysfunction. In the case of sudden
death, ventricular fibrillation has been observed
to be high, and a sharp disturbance of pumping
function of the left ventricle and an increase in
pressure in the cavity contribute to its appearance
[4]. Comprehensive introduction of highly
informative instrumental methods of cardiac
examination,
first
of
all,
ehodoppler
cardiography, makes it possible to regulate the
idea of cardiomyopathy as a nosological unit [3].
According to European experts, the diagnostic
criteria of DCMP are [7] left ventricular ejection
fraction (LV ejection fraction) less than 45%
(according to echocardiography) or fraction
shortening of anterior left ventricular size less
than 25%. By results of genetic researches of
some scientists, in the development of idiopathic
DCMP, it has been established that family
predisposition, mainly on autosomal-dominant
inheritance. Autosomal recessive X-linked and
mitochondrial forms of the disease are also
found. Acute myocarditis plays a role in the
development of DCMP, when first myocardium is
affected and then chronic inflammation develops,
which in turn leads to remodelling of the heart
and its dysfunction (post-inflammatory DCMP)
[5,9]. It should be noted that when diagnosing
idiopathic DCMP it is necessary to take into
account its secondary origin on the background
of systemic blood disease, kidney pathology
ISSN 0975-2366
DOI:https://doi.org/10.31838/ijpr/2020.12.04.099
Dilorom Akhmedova et al / Differential diagnostic criteria for dilatational cardiomyopathy and
nonreumatic myocarditis in children
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International Journal of Pharmaceutical Research | Oct - Dec 2020 | Vol 12 | Issue 4
(uremic cardiomyopathy), on the background of
abnormal development of the heart and large
vessels (Gerland Blount White syndrome) and
inflammatory diseases of the main vessels,
mitochondrial diseases, which requires additional
methods of research [6,10].The clinical picture of
DCMP is variable and determined mainly by the
severity
of
circulatory
disorders.
The
hemodynamic disorder is a consequence of
significant reduction of myocardial contractility
and cardiac pumping function. First of all, the left
ventricle, which is accompanied by an increase in
pressure in the heart chambers, their dilatation
with subsequent development of stagnation in the
small and large circulation circle.Heart Failure
Clinic depends on the degree of stagnation in the
small and large circulation circle, in the early
stages is determined mainly by the signs of left
ventricular failure with progressive left ventricular
failure (with a clinical picture of pre-edema and
pulmonary edema), as the progression of heart
disease severity is joined by right ventricular
failure
(hepatomegaly,
oedema
syndrome).Considering the severity of clinical
symptoms,
the
progression
of
clinical
manifestations in the dynamics of the disease and
the formidable complications that often lead to
death, early diagnosis and differential diagnosis
of DCMP in children is a crucial problem in
clinical pediatrics in general and in pediatric
cardiology. Based on the above, this scientific
research aimed to determine clinical, functional
features of dilatational cardiomyopathy and
nonreumatic myocarditis in children.
RESEARCH MATERIALS AND METHODS
We examined 60 children with DCMP and 40
children with non-rheumatic myocarditis aged
from 2 months to 18 years who were hospitalized
at the cardioreumatology department of the
Republican Specialized Scientific-Practical Medical
Centre for Pediatrics of the Ministry of Health. The
control group consisted of 30 practically healthy
children. Analysis of anamnesistical and objective
data showed that children's DCMP was 16.6±3.4
months old on average. The diagnosis was made
based on complaints, anamnesis data (obstetric
history of the mother, history of the child's life and
illness, past diseases, nature of the course and
duration of the disease) and clinical and
functional data (ECG, echocanalysis, Holter ECG
monitoring), laboratory (general hematological
analysis, biochemical blood analysis with the
determination of cardio specific markers -
creatine kinase, lactate dehydrogenase) and
instrumental (chest X-ray, multispiral computer
tomography of the chest) examination methods.
At the time of the examination, the age, sex,
height and divweight of the child were taken
into account. Body surface area (PPT, m2) and
div mass index (BMI) were calculated based on
div length/height and div weight. The PPT was
calculated using the Du Bois formula: PPT = M
0.425 x P 0.725 x 71.84 x 10 -4, where M is
div weight (kg), P is div length/height (cm);
BMI is calculated using the formula: BMI = M/P2
(kg/m2). ECG was carried out as planned to
patients
at
each
hospitalization
in
cardioreumatology department, both at the
primary examination and repeated hospitalization
in the department on the Aplio-500 ultrasound
device ("Toshiba", Japan) with 3.0-6.5 MHz sector
sensors. EchoCG was performed according to
standard methods following domestic and foreign
guidelines
and
recommendations.
Two-
dimensional
echocardiography
with
the
determination of echometric indicators was used.
Left ventricular myocardial contractility was
assessed by the Teicholtz or Simpson ejection
fraction (LV) and left ventricular myocardial
shortening fraction (LV) [6].
RESULTS AND THEIR DISCUSSION
In children's practice, differential diagnostics of
DCMP with other diseases, especially with non-
rheumatic carditis, is relevant. The problems of
our research were the questions of early
diagnostics of DCMP with studying the
peculiarities of clinical manifestations and
structural-functional state of the cardiovascular
system. The study of the clinical course of DCMP
and NM showed that both dilatational
cardiomyopathy and myocarditis had many
similarities in clinical picture and complaints in
general.
Fig.1: Clinical features of children with DCMP and NM (%)
Dilorom Akhmedova et al / Differential diagnostic criteria for dilatational cardiomyopathy and
nonreumatic myocarditis in children
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International Journal of Pharmaceutical Research | Oct - Dec 2020 | Vol 12 | Issue 4
The occurrence and nature of clinical symptoms
were found to depend on the degree of
cardiovascular insufficiency. The most typical
clinical manifestations for children with DCMP
were: rapid fatigue in (100%), swelling of the
extremities in (66.6%), shortness of breath in
(42%), cough in (83.3%). For children with
nonreumatic myocarditis, the more typical clinical
manifestations were: increased div temperature
(70%), cough (20%), rapid fatigue (100%) (Fig.1).
We also assessed hemoglobin levels in children
with DCMP and NM. The analysis of the
conducted researches has shown, that the
average level of hemoglobin in children with
DCMP (103,2±1,7 g/l, p<0,01) and with NM
(99,4±1,9 g/l, p<0,01) corresponded to anemia
of a mild degree and was reliably lower in
comparison with indicators of practically healthy
children. The average hemoglobin level in
children with DEMP and NM did not significantly
differ (Table 1).
Table 1: Hemoglobin level assessment
Almost
healthy
children n=30
Children
with DCMP
n=60
Children
with
NM
n=40
P
Р
1
Р
2
Hemoglobin level
(g/l)
121,1±0,45
103,2±1,7
99,4±1,9
<0,01
<0,01
>0.05
Note: P - reliability of differences between
indicators of children with practically healthy
children and children with DCMP; P
1
- reliability of
differences between indicators of children with
almost healthy children and children with NM; P
2
-
reliability of differences between indicators of
children with DCMP and children with NM. The
blood electrolyte levels in the children examined
were determined for CNS prediction.
Table 2: Blood electrolytes in children with DCMP and NM
Indicators
of
Electrolytes in blood
Almost
healthy
children n=30
Children
with DCMP
n=60
Children with
NM n=40
P
Р
1
Р
2
Potassium (
К
+
) (3,4-
4,7 mmole/l)
4,43±0,09
4,73±0,11
4,27±0,12
<0,05
>0,05
<0,05
Natrium (Na
+
) (136-
145 mmole/l)
141,68±0,84
135,12±0,9
7
137,82±0,97
<0,01
>0,05
>0,05
Calcium (Ca
2+
) (2,25-
2,75 mmole/l)
2,25±0,02
1,81±0,04
1,82±0,04
<0,01 <0,01 >0,05
Note: P - reliability of differences between
indicators of children with practically healthy
children and children with DCMP; P
1
- reliability of
differences between indicators of children with
almost healthy children and children with NM; P
2
- reliability of differences between indicators of
children with DCMP and children with NM.
Analysis of blood electrolytes showed (in Table 2)
that children with DCMP, compared to both
children with practically healthy children and
children with NM, had reliably increased
potassium levels (4.73±0.11.p<0.01), and
sodium
levels
were
reliably
decreased
(135.12±0.97.p<0.01), which is typical for
congestive heart failure. Calcium level has been
reliably reduced at children both with DCMP
(1,81±0,04, p<0,01) and with NM (1,82±0,04,
p<0,01) concerning indicators of practically
healthy children.As is known, one of the most
sensitive markers of acute inflammation is C-
reactive protein (CRP). To differentiate the genesis
of DCMP and NM, a comparative analysis of DRR
indicators in children with DCMP and NM was
carried out.
Table 3:C-reactive protein parameters in children with DCMP and NM
Almost
healthy
children n=30
Children with
DCMP n=60
Children with
NM n=40
P
Р
1
Р
2
C-reactive protein
(g/l)
2,1±0,4
4,00±0,4
6,0±0,3
<0,05 <0,01 <0,05
Note: P - reliability of differences between
indicators of children with practically healthy
children and children with DCMP; P
1
- reliability of
differences between indicators of children with
almost healthy children and children with NM; P
2
- reliability of differences between indicators of
Dilorom Akhmedova et al / Differential diagnostic criteria for dilatational cardiomyopathy and
nonreumatic myocarditis in children
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International Journal of Pharmaceutical Research | Oct - Dec 2020 | Vol 12 | Issue 4
children with DCMP and children with NM. As can
be seen from Table 3, the level of C-reactive
protein in children with NM (6.0±0.3 g/l) was
significantly increased compared to children with
DCMP (p<0.05) and children with practically
healthy children (p<0.01). The level of DRR in
children with DCMP was also higher than in
almost healthy children but to a lesser extent. All
patients were diagnosed with heart failure
syndrome at the time of examination. In the
group of children with DCMP, the CI II B st. (III EF)
was detected more often (36,6%), while in the
group of children with NM, the highest
percentage was registered at CI A I art. (II EF)
(37,5%). It is worth mentioning that in the group
of children with DCMP, the insufficiency of blood
circulation was expressed and the degree of
severity was higher than that of children with NM.
Thus, children with CI DCMP st. (I EF) did not
have it, while in children with NM it was 35,0%.
At the same time, the CI III st. (IV EF) was
observed in 33,3% of children with DCMP, while
in children with NM, this degree was not
diagnosed.The X-ray examination revealed an
increase in the heart size, mainly due to the left
wings, in 66.7% of children with DCMP, while the
total expansion was recorded in 13.3% of
children, cardiothoracic index being on average
63.3±0.5%. In children with NM, the
cardiothoracic index averaged 59.6±0.3%.
The phenomenon of excitement was more
frequent in 3 (7.5%) children with NM than in the
comparison group (3.3%). The frequency of
atrioventricular blockade of different degrees of
severity did not differ in the comparison groups.
In children with DCMP AV, the siege of 2-3
degrees occurred in 6 (10%) children, while in
children with NM no blockade was registered.
Violations of ventricular depolarization were
observed in the main group more often than in
the comparison group 2 (5%), with 6 (10%).
Absence or rare cases of extrasystoles were
mainly recorded, while frequent extrasystoles were
present in single cases. Paired ventricular
extrasystoles were found in 5 (8,3%) patients with
DCMP and 2 (5%) children with NM. QT interval
prolongation was observed in 10% of patients
with DCMP, and there were no deviations in the
comparison group. Echo CG in children with
DCMP and NM revealed: cardiac chamber
dilation, systolic dysfunction with reduction of
ejection fraction from 40% to 16%, regurgitation
on
mitral
valve
and
tricuspid
valve.
Echocardiographic signs in the examined children
are presented in Tables 4 and 5.
Table 4: Echocardiographic signs in children with DCMP and NM
Echocardiographic signs
Children
with
DCMP (n=60)
abs. (%)
Children with
NM (n=40)
abs. (%)
Valve regurgitation (TV and MV )
60 (100%)
20 (50%)
Systolic dysfunction
60 (100%)
40 (100%)
Emission fraction reduction below 40%
60 (100%)
-
Left ventricular wall hypokinesia (LV)
60 (100%)
40 (100%)
Paradoxical movement of the inter ventricular septum (IVS)
20 (33,3%)
-
Hypertrophy with dilatation
5 (8,33%)
-
Studies have shown that in children with DCMP,
all echocardiographic disorders prevailed over
myocarditis. Thus, all examined children with
DCMP showed systolic dysfunction, reduction of
ejection fraction below 40%, left ventricular wall
hypokinesia, valve regurgitations (MV and TV).
Such disorders as systolic dysfunction, reduction
of ejection fraction up to 40%, hypokinesia of LV
walls in (100%) children with NM were revealed.
Paradoxical movements on IVS have observed
only in 20 (33.3%) children with DCMP (Table 4).
Table 5: Echocardiographic signs in children with DCMP and CI
Echocardiographic signs Children with DCMP
n=60
Children with NM n=40
Level of reliability
Р
FDV LV
(мл)
108,8±9,04
60,9±4,4
<0,01
FDS LV
(мм)
45,70±1,35
39,65±1,2
<0,01
ФВ (%)
31,32±1,64
51,05±0,94
<0,01
Note: P - reliability of differences between comparable groups
As can be seen from Table 5, in children with
DCMP, statistically reliable (p<0.01) prevailed
FDV LV (108.8±9.04 ml) and FDS LV
(45.70±1.35 mm). These indicators suggest that
Dilorom Akhmedova et al / Differential diagnostic criteria for dilatational cardiomyopathy and
nonreumatic myocarditis in children
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International Journal of Pharmaceutical Research | Oct - Dec 2020 | Vol 12 | Issue 4
the signs of heart failure were more severe in
children with DCMP. The FS was found to be
significantly lower in children with DCMP
(31.3±1.6%,
p<0.01).
The
results
of
echocardiographic studies showed that in children
with DCMP the finite-diastolic volume of the left
ventricle reached from 94 ml to 206 ml, which
was associated with an increase in its filling
pressure and pronounced dilatation of the left
ventricle, which was accompanied with varying
degrees of relative insufficiency of mitral in cases
and tricuspid valves. According to our data, an
increase in the finite-diastolic volume of the left
ventricle over 12 mmHg was observed in 40% of
children, and systolic and diastolic pressure in the
pulmonary artery over 30 and 12 mmHg,
respectively. This was accompanied by an
increase in right ventricular filling pressure over 6
mmHg. Right ventricular dilatation in 10% of
children was accompanied by a dilatation of
hollow and hepatic veins, which is typical for
stagnation of blood in a large circulation circle.
By predominant localization of myocardial lesion
by echocardiographic criteria, the children were
divided into six variants of DCMP:
Fig.2: Distribution of children with DCMP according to echocardiographic variants %)
As can be seen from Picture 2, children were
subdivided into six variants of DCMP according to
echocardiographic criteria by predominant
localization of the lesion in myocardium: 14
(23.3%) children with variant 1 - with isolated left
ventricular lesion; 20 (33.3%) children with option
2 - with left atrium and left ventricular lesions; 6
(10%) children with variant 3 - with an effective
change of right heart regions; 10 (17%) children
with the 4th variant - with dilatation of both
ventricles; 8 (13,3%) children with the 5th variant
- with dilatation of all four heart chambers; 2
(3,3%) children with the 6th variant - with
significant dilatation of both atria with minimal
changes in the morphofunctional state of the
ventricles.In
children
with
the
3rd
echocardiographic
variant
of
DCMP,
differentiation with arrhythmogenic dysplasia of
the right ventricle was made. Among
echocardiographic variants 1 and 2 variants
(57,1% of children) were the most frequent, which
are manifested by left ventricular and left atrial
dilatation. In such children, differentiation of
DCMP with non-reumatic myocarditis was made.
Among them, 23.3% of children had positive
dynamics with improvement of functional indices,
namely, improvement of myocardial contractility,
increase of discharge fraction (up to 45% in
dynamics), reduction of FDV LV. In 1 child, the
signs of heart failure were eliminated with the
restoration of cardiac pumping function (EF 40%,
in dynamic 60%). That was the reason for
changing the initial diagnosis of DCMP to non-
reumatic myocarditis later. In 5 (8.3%) children, a
fatal
outcome
was
noted
despite
the
comprehensive therapy as a result of the growing
heart failure and arrhythmic syndrome, which is
one of the most formidable complications of
DCMP. The dilatation of all four heart chambers
(5th variant of DCMP) was visualized on the
EchoCG in children of this group.
3.33%
13.33%
17%
10%
33.33%
23%
0.00% 5.00% 10.00%15.00%20.00%25.00%30.00%35.00%
With a significant dilatation of both atria.
With the dilatation of all four heart cells.
With dilatation of both ventricles.
With an overriding change in the right side of
the heart.
With lesions of the left atrium and left ventricle.
With isolated left ventricular lesion
Children with DCMP (n=60)
Dilorom Akhmedova et al / Differential diagnostic criteria for dilatational cardiomyopathy and
nonreumatic myocarditis in children
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International Journal of Pharmaceutical Research | Oct - Dec 2020 | Vol 12 | Issue 4
(a)
(b)
Fig.3: Echocardiogram b-go A., 2 years. Diagnosis: DCMP: A - total hypokinesia of LV walls; B -
dilatation of all heart cells in four-chamber position.
Echocardiographic indices of the 1st and 2nd
variants of DCMP are similar to those of acute
myocarditis, especially in young children.
Distinctive signs in children with DCMP are
progressive course of cardiac insufficiency and
refractoriness of anti-inflammatory therapy, i.e.
progressive reduction of myocardial contractility,
lesions and other cardiac chambers to the total
expansion of all cardiac chambers.
Thus, the comparative analysis has shown that the
development of NM is mainly due to viral etiology
and the process is inflammatory. DCMP is
characterized by a variety of echocardiographic
manifestations, which can be grouped into 6
echocardiographic variants. Distinctive features of
both
blood
electrolyte
composition
and
echocardiographic features in children with
DCMP as compared to children with HP are
progressive course of heart failure and refractory
anti-inflammatory therapy, i.e. progressive
reduction of myocardial contractility, lesions and
other heart chambers to total expansion of all
heart chambers.
To determine the presence of heart failure and
assess its severity, much attention is paid to the
search for objective criteria, which include the
determination of the blood content of cardiac
markers. These included creatine phosphokinase
(CPK), lactate dehydrogenase (LDH), brain
natriuretic peptide (NT-pro BNP), and the de
Rhytis AST/ALT ratio, which is normal at 1.5. One
of the objectives of this scientific research was to
determine the significance of sodiumuretic
peptide in early diagnosis and prognosis of
chronic heart failure in dilated cardiomyopathy in
children, as well as in differential diagnosis with
nonreumatic myocarditis.
Table 6: Biochemical marker data in children with DCMP and NM
Biochemical markers
Almost
healthy
children n=30
Children
with DCMP
n=60
Children with
NM n=40
P
Р
1
Р
2
Creatinephosphokinae
(CPK)
53±4,3
188,7±18
255,9±14,9
<0.01
<0.01
<0,01
Lactate dehydrogenase
(LDH) (225-450 ME/l)
175±7.3
476,8±28,9
476,9±43,8
<0.01
<0.01
<0,01
Alaninterransfer (ALT)
(<40)
20,03±3,85
31,03±3,8
19,9±1,85
<0,01 <0,01
<0,01
Aspartartaransfer (AST)
(<35)
17,5±7.3
50,78±4,7
25,67±2,1
<0,01 <0,01
<0,01
de Ritis AST/ALT ratio
(N<1,5)
1,2±0,03
1,9±0,08
1,48±0,09
<0.01
<0.01
<0,01
Note: P - reliability of differences between
indicators of children with practically healthy
children and children with DCMP; P
1
- reliability
of differences between indicators of children with
almost healthy children and children with NM; P
2
- reliability of differences between indicators of
children with DCMP and children with NM.
The analysis of research results showed (Table 6)
that the following blood biochemical parameters
were reliably increased in children with nerve
Dilorom Akhmedova et al / Differential diagnostic criteria for dilatational cardiomyopathy and
nonreumatic myocarditis in children
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International Journal of Pharmaceutical Research | Oct - Dec 2020 | Vol 12 | Issue 4
myocarditis: LDH - 255.9±14.9 ME/l (p<0.01);
LDH - 476.9±43.8 ME/l (p<0.01); de Ritis
AST/ALT ratio - 1.48±0.09 (p<0.01). The
expressed increase in all three indicators
prevailed in 30% of children with NM, while
53.3% of children with DCMP had an increase
more often than one in three biochemical
indicators.
The level of sodiumuretic peptide (NT-pro BNP) at
all stages of CI was determined to assess the
prognosis of heart failure in children with DCMP
and
NM.
Fig.4: NT-proBNP content in children with DCMP and NM, depending on the CI stage.
The analysis of blood NT-proBNP results showed
(pic.4) that children with DCMP were significantly
elevated from CI III Art. (IV EF) was up to 38000
pg/ml, while in children with non-reumatic
myocarditis with CI III art. (IV EF) was up to 1200
pg/ml (Fig.4).
CONCLUSION
As can be seen, the most expressed increase of
biochemical markers is observed at DCMP, which
is confirmed by unfavorable outcomes in the
process of progression of this pathology in
children. All this determines in the presence of risk
factors for the development of DCMP, along with
functional studies it is necessary to determine
cardio specific markers - creatine phosphokinase,
lactate dehydrogenase, as well as a brain
natriuretic peptide. Determining the level of NT-
proBNP in plasma helps to assess the severity of
chronic heart failure, to predict further
development of the disease, as well as to assess
the effectiveness of therapy.
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0
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