Журнал «Здоровье ребенка» 2 (45) 2013

It is well-known that celiac disease is one of the most common genetically-determined diseases occurring among children, which is characterized by chronic disorders of digestive organs. Disturbance of metabolic processes, typical of this disease, may cause disorders not only of digestive organs, but also of many other organs and systems, in particular of the cardiovascular system [1]. The latter plays a crucial role in normal life activity. Its functional characteristics are closely related to the functioning of the body as a whole, therefore CVS is considered to be a universal indicator of an organism’s adaptation activity on the whole [2, 3]. It is frequent that CVS changes make the affected children, their parents and doctors no less anxious than bowels disorders themselves. However, there are only few publications dealing with characteristics of CVS functioning in children with celiac disease, which contributes to the relevance of this research. Thus, the objective of this research is to study CVS functional status in children suffering from celiac disease.

Research materials and methods. 19 patients with celiac disease aged from 9 months to 17 years who were treated at the gastroenterological department of Kharkiv regional children’s clinical hospital in the period from 2006 to 2009 were examined. The majority of the patients examined (р<0.01) had typical form of celiac disease (17 children – 89.5%). Diagnosis was verified based on the determination of antigliadin antibody titer, tissue transglutaminase rate and morphological structure of the small intestine mucous membrane.  

Electrocardiography (ECG) (Bioset-6000 electrocardiograph, Germany), Doppler echocardiography (DpECHOCG) (AU 3 Partner ultrasound scanner, make Esaote Biomedica, Italy) were applied for CVS functional status examination along with thorough clinical monitoring. Functional status of the autonomic nervous system (ANS) was assessed based on the measurements of initial vegetative tonus (according to the chart drawn up at the department of visceral pathology of the First Moscow Medical Institute) [4]. Statistical treatment of data was performed using Microsoft Excel-97 software.

Research results and their discussion. Different pathology was diagnosed at early stages of disease manifestation in children; most frequently, malabsorption syndrome occurred in 26.9% children, anaemia in 30.8% and failure to thrive in 19.2% of patients.

Patients had many different complaints at hospitalization. The patients mostly complained of abdominal pain (89.5% ±7.0, р<0.001), loss of appetite (31.6%±10.6), undue fatigability (21.1%±9.3), vomiting (26.3%±10.1), frequent frothy bowel movement (26.3%±10.1); one fifth of patients had a tendency for constipation. 2 (10.5%) school-age children complained of shooting heart pain after physical and emotional tension. Thus, complaints pertaining to the nervous and cardiovascular systems were frequently observed besides complaints typical of digestive system pathologies.

In the course of medical history analysis it was established that 70% of mothers had pathological pregnancy. In most mothers with abnormal obstetric history (55.5%), adverse factors influenced the fetus during the first half of gestation period. Abnormal labour (weak labor activity, prolonged, impetuous, medicine-stimulated, etc.) occurred in 46.2% of mothers. One in five children had chronic hypoxia during the prenatal period, 11.5% had birth trauma, 7.7% were diagnosed with prenatal hypotrophy.

1/4 of infants had anxiety, irritability, sleep disturbances, and loss of appetite; 62% of children had early artificial feeding. 4 (15.4%) children were diagnosed with atypical dermatitis. 2/3 of patients had a high infection index. Lack of lactose occurred in 2 (7.7%) children. 3 (11.5%) patients had antibiotic-associated diarrhea. The psychological climate in the families of 11.5% patients is unfavorable.

1/3 of children have complicated family medical history. Relatives of 10 (38.5%) patients suffered from gastrointestinal disturbances, 15.4% of parents had diabetes mellitus, and 3 (11.5%) persons had atypical dermatitis. Close relatives of 6 (23%) patients suffered from CVS diseases.

Skin pallor (89.4%±7.1, р<0.001), periorbital shadows (31.5%±10.6), tongue plaque (73.7%±10.1, р<0.05), abdomen painfulness mostly on epigastrium palpation (63.2%±11.1, р<0.01) and in the right subcostal area (36.8%±11.1) were present during physical examination. Emotional lability occurred in 52.6%±11.4 children, signs of connective tissue dysplasia in 57.8%±11.3, and polymicroadenia in 52.6%±11.4.

The following autoimmune disorders associated with digestive organs diseases in the setting of congenital metabolism pathology were diagnosed: liver cirrhosis in 1, diabetes mellitus in 1, autoimmune thyroiditis in 1, and fatty hepaosis in 1 child.

Hemogram gave evidence of anemia in 47% of children. Signs of blood clotting developed as a result of multiple vomiting were identified in 32% of children. Blood biochemical test had the following results: cholesterol and beta-lipoproteid rates were decreased in 53% of children. 32% of patients had water-electrolytic exchange disorders. Microscopic test of bowel had the following results: steatorrhea in 32%, creatorrhea in 47%, and amylorrhea in 58% of children.

Detailed analysis of clinical data pertaining to CVS (Table 1) proved that most patients had systolic murmur of functional nature (chiefly at the top and/or in 4^th intercostal space in the breast bone on the left), one forth of patients had murmurs in the first or both heard sounds with the borders of relative cardiac dullness being within the normal range. Heart rate was normal in only one third of children; moderate bradycardia occurred more frequently than tachycardia; Systolic BP was normal in most patients while diastolic BP was slightly decreased.

ECG tests in children proved that only 5 (21.1%) of patients had no changes on the ECG. All other children had different abnormalities of heart rate, cardiac conduction and excitability, and repolarization processes. Moderate prolongation of the QRS interval occurred in 15.7%±8.3 patients, of the QT interval in 21.0%±9.3, shortening of the QT₁ interval occurred in 26.3%±10.1, widening of the T wave in 36.8%±11.1, siaplacement of the ST segment above isoline in 31.6%±10.6, below isoline in 15.7%±8.3 of patients. Therefore, patients’ ECG changes reflected disturbances of ventricular repolarization processes. Examining patients’ automatism functions based on ECG results showed that nomotopic heart rate irregularities were prevailing (occurring in 52.6%±11.4), among which sinus tachycardia was prevalent (in 40.0%±16.3). Heterotopic arrhythmia (right upper auricular rhythm, wandering pacemaker, extrasystole) occurred twice as seldom (in 26.3%±10.3).

According to ECG results, none of the patients had signs of organic heart abnormalities, which was proved by ECHOCG, identifying minor structural heart abnormalities and moderately expressed morphological changes of cardiac chambers and major vessels in a number of patients. Prolapse of mitral valve leaflets (36.8%±11.1) and abnormal cords of left ventricle (LV) (31.6%±10.6) occurred most frequently from among minor structural heart abnormalities.

Morphological changes of cardiac chambers and major vessels in children with celiac disease are described in Table 2. They occurred in three patients only: one child had minor enlargement of left heart, two children had minor enlargement of right heart. Sizes of major vessels and pressure gradients on their valves were within the normal range. Average pressure in the pulmonary artery trunk was 14 to 20 mm Hg.

Analysis of central hemodynamics (CH) parameters showed that most patients (8 children, 66.7%) had normodynamia (СІ = 99.2% of the normal rate) with normal heartbeat (103.4% of the normal rate) and ejection fraction (EF) (97.6% of the normal rate) rates. 3 patients (25.0%) had hypodynamic CH mode (СІ = 69.1%±11.3 of the normal rate). These were patients with severe celiac disease of typical form, determined by dyspeptic syndrome (vomiting, frequent bowel movements) with з diselectrolytic disorders. One child (8.3%) with typical celiac disease combined with moderately severe deficiency anaemia had hyperdynamic CH mode (СІ = 119.8% of the normal rate) due to tachycardia (heart rate = 125.1% of the normal rate), caused by activation of sympathetic nervous system (probability of prevalence of sympathetic manifestations (Рс) – 76.8% [5]).   

            Myocardial dysfunction occurred in 7 (58.3%) children. Systolic myocardial dysfunction (deterioration of contractile and pumping heart functions) occurred in 2 (16.6%) patients. One of them (9-year-old child) had hypodynamic CH mode with low EF and moderate bradycardia, the other child (3 years old) had normodynamic CH mode with moderate intraventricular septum hypokinesia, tendency for bradycardia and parasympathicotonic initial vegetative tonus.

            Transmitral flow disorder indicating diastolic myocardial dysfunction occurred in 5 (41.7%) of patients. 3 of them (60.0%) had restrictive type, 2 of them (40.0%) had pseudonormalization of the mitral flow. None of the patients had abnormal (hypertrophic) myocardial relaxation. This may be explained by long history of the disease (4.8±3.6 years) and by the fact that coeliac disease was manifested during the child’s first year (in 2 of 5 patients), which accounts for abnormalities in myocardial elastic properties, typical of the restrictive type and pseudonormalization of the mitral flow. Patients with restrictive type of diastolic dysfunction had probable increase in correlation of peak rates (Е/А=2.36±0.09, р<0.05), reduction of left ventricle early filling slowing-down time (SD) to 0.11±0.008 sec and isovolumic relaxation time (IVRT) to 0.053±0.004 sec (р<0.05).

Therefore, diastolic myocardial dysfunction occurred 2.5 times more frequently than systolic dysfunction in our patients. This may be caused by the influence of electrolytic and phosphoric-calcium exchange disturbances (hypophosphatemia, hypomagnesemia, hypocalcemia, and hypercalcinuria) associated with malabsorption syndrome on heart chambers compliance and LV diastolic filling. Such disturbances occurred in 6 (31.5%) patients, including all children with diastolic myocardial dysfunction. Besides, development of the latter contributes to disease duration. This is confirmed by the results of correlation analysis conducted by us. It was established that there is a strong correlation between the type of diastolic dysfunction and diastole time and disease duration (r = +0.78, r = +0.84 respectively), which indirectly shows the probability of diastolic dysfunction progression with the loss of myocardial compliance in the course of disease without appropriate cardiometabolic support and correction of water-electrolytic exchange disorders.

Transmitral flow parameters did not deviate from the normal range in 5 (41.7%) patients. These were children who were monitored at the stage of clinical and laboratory disease remission. No clinical and instrumental signs of heart failure were established in any patients.

Conclusion. Most children (78.9%) suffering from celiac disease had CVS functional changes (secondary cardiomyopathy, vascular dystonia) manifested by the complaints of heart pain, heart murmurs, systolic murmur of functional nature, moderate abnormalities of heart and blood pressure rates, abnormalities on the ECG (mostly heart rhythm (chiefly nomotopic) and repolarization processes irregularities), echocardiographic signs of central hemodynamics disturbances and myocardial dysfunction (chiefly diastolic). Metabolic disorders due to malabsorption syndrome and CVS neurohumoral regulation disturbances due to vegetative dysfunction are important factors of cardiovascular syndrome development in children with celiac disease. Absence of CVS-related complaints does not rule out secondary cardiomyopathy and vascular dystonia, therefore, it is necessary to perform instrumental examinations (ECG, ECHOCG, DpECHOCG) and determine ANS functional status in addition to detailed CVS examination. Cardiovascular system disorders in children with celiac disease account for the necessity of timely correction of water-electrolytic disorders and prescription of cardiometabolic treatment.