CC BY
24
Section 2. Medical science
Akhmedova Dilorom Ilkhomovna, Director of the Republican Specialized Research-Practical Medical Center of Pediatrics, Republic of Uzbekistan Ruzmatova Dilfuza Mirzabaevna, researcher, Republican Specialized Research-Practical Medical Center of Pediatrics, Republic of Uzbekistan E-mail: ludmilamedlib@mail.ru Ibragimov F. F.,
researcher, Republican Specialized Research-Practical Medical Center of Pediatrics, Republic of Uzbekistan
Akhmedova S. B.,
researcher, Republican Specialized Research-Practical Medical Center of Pediatrics, Republic of Uzbekistan
CLINICAL-FUNCTIONAL FEATURES OF DILATED CARDIOMYOPATHY IN CHILDREN IN DEPENDENCE ON MEDICAL-BIOLOGICAL FACTORS OF DEVELOPMENT
Abstract. There have been studied clinical and functional characteristics of dilated cardiomyopathy in 42 children at the age of 2 months to 18 years, hospitalized into the cardiorheumatologic department of the Republican specialized scientific-practical medical center of pediatrics. With regard to predominant localization of the lesion in the myocardium according to echocardiographic criteria in children there were defined six variants of dilated cardiomyopathy with prevalence of variants with damage of the left atrium and left ventricle (33.3%) and with isolated damage of the left ventricle (23.8%). For favorable outcome of these diseases there is required early diagnosis and timely onset of therapy.
Keywords: dilated cardiomyopathy, clinical features, functional changes, children.
According to the current notions the dilatational cardiomyopathy is considered as cardiac muscle disease of unknown or unclear etiology, characterizing by cardiomegaly due to dilatation of the heart cavities, particularly cavity of the left ventricle, progressing attenuating of the myocardium contractility, suddenly developing and progressing heart insufficiency, arrhythmic and thromboembolic syndromes with ending frequently by sudden death [1]. Dilatational cardiomyopathy is characterized by continuously progressing development, occupies leading positions in the structure of disability and mortality of children, appeared to be main cause of the formation of chronic cardiac insufficiency at the childhood [2]. The prevalence of dilatation cardiomyopathy varied from 40 cases per 100000 a year in Europe. This disease is met more frequently in boys than in girls. The specific weight of dilatational cardiomyopathy among the other cardiomyopathies accounts for 60% [3]. The frequency of sudden mortality among children with di-
latational cardiomyopathy accounts from 1.5% to 4%, in the majority of cases the cause of lethal outcome is arrhythmia. The cardiac rhythm disorders have both bradycardia (atrioventricular blockade) and tachycardia character (unstable ventricular tachycardia). Polymorphic gastric extrasystole is related to the risk factors of the sudden death. At the same time the disorders of the heart rhythm are not independent risk factors of the sudden death, because they closely connected with left ventricle dysfunction. In case of sudden death there is noted high frequency of ventricle fibrillation, its appearance connects with sharp disorder of the left ventricle pumping function and pressure arising in its cavity [4]. The wide introduction of the high informative instrumental methods for heart investigation, first of all, echodopplercardiography allows putting in good order the knowledge about cardiomyopathy as nosological notion [3]. Diagnostic criteria of DCMP, by opinion of European experts, are [4] left ventricular (V) ejection fraction less than 45%
(by echocardiography) or fraction shortening ofthe anteroposterior size of the left ventricle less than 25%. According to the results of genetic investigations of a number of scientists, in the development of idiopathic DCMP there was established family predisposition, predominantly by autosomal-dominant inheritance. There were also met autosomal-recessive Z-linked and mitochondrial forms of disease. In the development of DCMP the acute previous myocarditis also plays a role, when firstly myocardium impairs, and then chronic inflammation occurred, which, in its turn, results in remodeling of heart and its dysfunction (postinflammatory DCMD) [5]. It should be noted that in the dominant majority of the family forms of DCMP the genetic disorders associated with autoimmune ones, and the viruses can act as a starting factor for development of DCMP in people with genetic predisposition. On the whole DCMP etiology remains to be unclear to the present time.
It should be noted that for making diagnosis of idiopathic DCMP it is necessary to take into account its secondary etiology on the basis of systemic blood diseases, kidney pathology (uremic cardiomyopathy), on the basis of malformations of heart development and large vessels (syndrome of Gerland Blount White) and inflammatory diseases of great vessels, mitochondrial diseases, that requires performance of the additional methods of investigation.
The right and timely making diagnosis of DCMP remains to be not simple task. The determination of diagnosis should be performed on the basis of all methods, beginning from anamnesis collection, clinical examination of patient and ending with results of non-invasive and invasive methods of study.
Clinical picture of DCMP is variable and is determined, first of all, by severity of blood circulation disorders. Hemodynamic disturbance is the consequence of the significant reduction of myocardium contractility and cardiac pump function, and first of all of the left ventricle, which is accompanied by increase in pressure in the heart chambers, their dilatation with following development of congestive evidences in the pulmonary and systemic circulation.
At the early stages, unfortunately, the disease progresses little or without symptoms. Sometimes heart impairment is found during ECG performance or in roentgen logical investigation due to pathology of bronchopulmonary system.
The first clinical sign of disease may be disorders of heart rhythm and thromboembolic syndrome (thromboembolism of the pulmonary artery and embolism in the artery of the systemic circuit of circulation, acute disorder of the cerebral circulation with evidences of stroke and myocardial infarction) [3; 6].
The clinical picture of heart insufficiency depends on the severity degree of congestive evidences in the pulmonary and systemic circulation, at the early stages of disease there are mainly signs of impair of the left departments of the heart with
progressing left ventricle insufficiency (with clinical picture before edema and edema of the lungs), during progressing of severity degree of heart the right ventricular insufficiency is added (appearance hepatomegaly, edema syndrome).
Taking into account severity degree of clinical symptom, progressing of clinical signs in dynamic of disease and hazardous complications, which frequently resulted in lethal outcome, the early diagnosis and differential diagnosis of DCMP in children is the actual problem of clinical pediatrics on a whole and children's cardiology.
On the basis of above presented the purpose of this research is determination of clinical, functional peculiarities of dilatational cardiomyopathy in children.
Materials and methods
We have studied 42 children with DCMP at the age of 2 to 18 years, admitted to the cardiorheumatological department of the Republican Specialized Research-practical Medical Center of Pediatrics of the Ministry of Health of the Republic of Uzbekistan. Control group included 30 practically healthy children.
Analysis of anamnesis and objective data showed that durability of DCMP in children, on the average, accounted 16.6 ± 3.4 months. Diagnosis was made on the basis of complaints, data of anamnesis (obstetrical mother anamnesis, anamnesis of life and child's disease, previous diseases, character of progressing and durability of disease). Clinical-functional (ECG, Holter monitoring, ECG), laboratory (general hematological analysis, biochemical blood analysis with determination of cardio specific markers of creatine kinase, lactatdehydrogenase) and instrumental (roentgenography of the chest, multispiral computed tomogram of the chest) methods of examination.
At the moment of investigation there were taking into account age, gender, height and mass of child body. On the basis of indicators of the body length/height and body mass there were calculated body surface area (BSA, m2) and body mass index (BMI). BSA was calculated by formulae Du Bois: BSA = M0.425 x P0.725 x 71.84 x 10-4, where M - body mass (kg), P-body length/height (cm); BMI - by formulae: BMI = M/P2((kg/m2). ECG was performed in patients according to plan order in every hospitalization in the department of cardiorheumatology, both in primary examination, and in repeated hospitalization in the department on the ultrasound apparatus Aplio-500 ("Toshiba", Japan) with sector sensors 3.0-6.5 MHz. EchoCG was made by standard methods with regard to native and foreign manual books and recommendations. There was used two-steps echocardiography with determination of echo metric parameters. The left ventricular myocardium contractility was evaluated by ejection fraction (EF) with method Teykholt or Simpson and fraction of the left ventricular myocardium shortening (FS) [7].
Results and their discussion more prevailed in children, age of mothers, which at the mo-
During investigations we studied medical-biological fac- ment of this child birth was above 35 years (52%). In 19% of
tors in development of DCMP in children. children the parents were closed relatives (Figure 1).
The study of biological factors showed that disease develops more often in boys (59.5%). Development of DCMP
Figure 1. Evaluation of medical-biological factors in children with DCMP
As it is known the birth of children with various diseases TORCH-infections (cytomegalovirus, herpes virus), events
and congenital anomalies, as well as the following their devel- of toxicosis in the second half of pregnancy: with preeclampsia
opment and health state dependent on development of preg- of stage 1 in 28.5%, with preeclampsia of stage II - in 19.0%,
nancy, character of labors and health state of their mothers. preterm deliveries - in 28.5% of mothers, as well as in 19% of
It should be noted that analysis of the obstetric anamne- mothers the cases of stillborn in the previous pregnancies, in
sis showed that mothers of children with DCMP in 88.2% of 30.9% of mothers the miss-carried fetus in the first and second
cases during pregnancy had ARVI, in 50% there were revealed trimester.
Children with DCMP(n=42)
Preeclampsia of the 1 half
Preeclampsia of the II half
Stillborns
Miss-carried fetuses
Preterm labors
28,50%
■ 19%
28,50%
30,90%
28,50%
5,00% 10,00% 15,00% 20,00% 25,00%
30,00% 35,00%
Figure 2. Evidences of the obstetric anamnesis of mothers of children with DCMP
Table 1.
Previous diseases in children with DCMP
ARVI
Chickenpok
Bronchopneumonia
Acute intestinal infections
Septic angina
Pyelonephritis
Children with DCMP
(n=42), Abs/%
42(100%)
20(47.6%)
11(26.2%)
6(14.3%)
5(11.9%)
4(9.5%)
Table 1 shows that in anamnesis of children with DCMP cases of ARVI are frequent and in significant part of patients -chickenpox. The following positions of the previous diseases in group of children with DCMP were occupied by bronchopneumonia, acute intestinal infections, angina and pyelonephritis.
The symptoms of congestive heart disease were one of the most typical sign at admission. In 25(59.5%) children with DCMP there were features of left ventricular insufficiency, in 17(%) - oftotal heart failure (of 3-4-functional class by NYHA).
In 3 children admitted into gastroenterological department with dyspeptic syndrome: with vomiting, loose stool and edemas in the lower extremities the diagnosis of DCMP was made by chance, in plan EchoKG investigations, in which there was found significant reduction of myocardium contractility - with reduced ejection fraction to 25%. In 6 children (14.3%) the first sign of DCMP was sudden death during the first 6 hours from the moment of appearance of the events of heart insufficiency in spite of performance of therapeutic measures, in 4 children (9.5%) by syncopal state in physical loading.
The diagnosis of postinflammatory DCMP was established in 14 children (31.8%). In this case from the onset of myocarditis to establishment diagnosis of DCMP the period about one year passed. The complete recovery in postmyocar-dial DCMP was registered in one child.
The roentgen logical investigation showed increase in heart sizes predominantly in the left parts in 57.1% o children, total enlargement was noted in 11.9% of children, cardiotho-racic index accounted for, on the average, 63.3 ± 0.5%.
On ECG in children there was prevailed rigidity of sinus rhythm with tendency to tachycardia in 30(71.4%) children, disorders of cardiac rhythm looking like extrasystole in 12 (28.5%) children, supraventricular tachycardia in 20(47.6%) children, disturbance of conductivity in form of blockade of the bundle of His, more often in the left anterosuperior branch in 36(85.7%) children, that was accompanied by sharp deviation of the electric axis to the left (EOS), as well as signs of hypertrophy of the left ventricle in 42(100%) children, and both ventricles in 10(23.8%) children.
With use of EchoCG in children with D CMP there was revealed dilation of the heart chambers, systolic dysfunction with reduction of the ejection fraction from 40% to 16%, regurgitation on the mitral valve and tricuspid valve. Echocardiographic signs in studied children are presented in (Table 2).
Table 2.- Echocardiographic signs in children with DCMP
Echocardiographic signs
Valve regurgitation (MV and TV)
Systolic dysfunction
Cardiac output reduction to 40%
LV hypokinetic wall motion
Interventricular septum paradoxical motions
Hypertrophy with dilatation
Children with D CMP n=42 (%)
42(100%)
42(100%)
42(100%)
42(100%)
20(47.6%)
5(11.9%)
Figyre 3. Distribution of children with DCMP in relation to echocardiographic variants
In all children with DCMP there was noted systolic dysfunction, reduction of ejection fraction lower than 40%, hyperkinesia of the walls of left ventricle. Paradoxical motions on the interventricular septum were noted in 20 (47.6%) children with DCMP.
The results of echocardiographic investigations showed that in children with DCMP the end-diastolic volume of the left ventricle achieved from 94 ml to 206 ml, that was connected with arising its pressure of filling and marked dilatation of the left ventricle which was accompanied with various degree of progressing of relatively insufficiency of mitral in a part of cases and in the tricuspid valves. On the basis of our data the increase in end-diastolic pressure in the left ventricle higher 12 mm Hg was observed in 57.1% of children, and systolic and diastolic pressure in the pulmonary artery, respectively, more than 30 and 12 mm Hg - in 42.9% of children. This was accompanied by increase in pressure of filling of the tight ventricle higher than 6 mm Hg. Dilatation of the right heart parts in 42.9% of children was accompanied by dilatation of vena cava and hepatic veins, that was characteristic for blood congestion in the pulmonary circle of blood circulation.
With regard to predominant localization of lesion in the myocardium according to echocardiographic criteria the children were subdivided into six variants of DCMP:
The distribution of children with DCMP in relation to echocardiographic variants is presented on fig.3. It may be seen that with regard to predominant localization of the lesion in the myocardium according to the echocardiographic criteria the children are subdivided into six variants of DCMP: 10 (23,8%) children with variant 1 - with isolated lesion of the left ventricle;
14(33.3%) children with variant 2 - with damage of the left atrium and left ventricle; 8(19%) children with variant 3 - with predominant change of the right heart parts; 4(9.5%) children with variant 4 - with dilatation of the both ventricles; 5(11.9%) children with variant 5 - with dilatation of all 4 chambers of the heart; 1 child (2.4%) with variant 6 - with significant dilatation of the both atriums in presence of minimum changes of the morphofunctional state of the heart ventricles. In children with 3 echocardiographic variants of DCMP there was performed differentiation with arhythmogenic dysplasia of the right ventricle. Among the variants of echocardiography the variant 1 and variant 2 were most often noted (57.1% of children), which manifest by dilatation of the left ventricle and left atrium. In these children there was performed differentiation of DCMP with nonrheumatic myocarditis. Of them in 23,8% of children on the basis of adequate complex therapy the positive dynamics with improvement of functional parameters, particularly -improvement of contractility of myocardium, increase in ejection fraction (in dynamics to 45%), decrease of end-diastolic volume of the left ventricle (LVEDV). In one child there was observed liquidation of the signs of the cardiac insufficiency with restoration of pump function of heart (EF 40%, in dynamics 60%). That is the reason for change of primary diagnosis of DCMP to nonrheumatic myocarditis in the following time. In 5(11.9) children there was noted lethal outcome in spite of performed complex therapy due to growing heart insufficiency and arrhythmic syndrome, that is one of the hazardous complications of DCMP. In the children of this group on the EchoCG dilatation is visualized in all four chambers of the heart (5 variant of the DCMP).
A B
Figure 4. Echocardiogram of patient A., of 2-year-old with DCMP: a) total hypokinesia of the LV walls; b) dilatation of all chambers of the heart in the four-chamber position
Echocardiographic parameters of variant 1 and 2 of DCMP have likeness with signs of acute myocarditis particularly in children of young age. The specific features in children with DCMP are progressing development of cardiac insufficiency and refractory of performed anti-inflammatory therapy, that is, progressing reduction of the myocardium contractility, lesions and other heart chambers to total broadening of all heart chambers.
Conclusions:
1. For development of children with dilatational cardiomyopathy the following factors have effect: on medico-biological factors - age of mother above 35 years, previously diseases in mother during pregnancy (predominantly of viral etiology), complicated pregnancy (eclampsia, abortion), preterm labor, hereditary predisposition to cardiomyopathy and closely related (congeneric) marriage;
2. For DCMP in children there are characteristic peculiarities in the functional parameters of the cardiovascular system: disorders of echocardiographic parameters such as systolic dysfunction, reduction of the ejaculation fraction lower than
45%, hypokinesia of the left ventricle wall. For children with DCMP (in 47.6% of cases) there were also characteristic paradoxal movements on the interventricular septum.
3. According to predominant localization of lesion in the myocardium and on the basis of echocardiographic criteria there are identified six variants of DCMP in children with prevalence of variants with lesion of the left atrium and left ventricle (33.3%) with isolated damage of the left ventricle (23.8%).
Thus, dilated cardiomyopathies are severe pathology of the childhood, for identification of which there is required careful study at early stages medico-biological factors, clinical evidences and data of the current methods of the functional diagnosis (ECG, EchoCG).In order to prevent development of DCMP in children it is necessary to make preventive methods for prevention of delayed labors, providing safe pregnancy and deliveries, prophylaxis and effective treatment of the diseases of viral etiology in mothers and children, and for favorable outcome of these diseases there is required early diagnosis and timely onset of therapy.
References:
1. Maron B. J., Towbin J. A., Thiene G., Antzelevich C. et al. Contemporary definitions and classification ofthe cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Yeart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2008; 113: 1807-1816. DOI 10.1161/CIRCULATIONAHA.106. 174287.
2. Lipshultz S. E., Cochran T. R., Briston D. A., Brown S. R., et al. Pediatric cardiomyopathies: causes, epidemiology, clinical course, preventive strategies and therapies. Future Cardiol 2013; 9; 817-848. DOI: 10.2217/fca. 13.66.
3. Wilkinson J., Landy D., Colan S., Towbin J., Sleeper L. A., Orav E. J., et al. Pediatric Cardiomyopathy Registry and Heart Failure: Key Results from the First 15 Years. Heart Fail Clin 2010; 6 (4): 401-413. DOI: 10. 1016/j. hfc. 2010.05.002).
4. Halliday B. P., Cleland J. G., Goldberger J. J., Prasad S. K. Personalizing risk Stratification for Sudden Death in Dilated Cardiomyopathy: The Past, Present, Future. Circulation 2017; 33(9): 888-909. DOI: 10.1161/ CIRCULA-TIONAHA. 116.027.
5. Guidelines for the study of familial dilated cardiomyopathies. Collaborative Research Group of European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy / L. Mestron [et. al.] // Eur. Heart J. 2000.- Vol. 20.-P. 93-102.
6. Mason J. W. Myocarditis and dilated cardiomyopathy: an inflammatory link / J. W. Mason // Cardiovasc. Res. 2013.-Vol. 60.- P. 5-10.
