CC BY
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Babamuradova Z. B., Shodikulova G. Z., Mirzaev O. V.
E-mail: shodikulovagulandom@mail.ru
TREATMENT OF PATIENTS WITH UNDIFFERENTIATED CONNECTIVE TISSUE DYSPLASIA IN MITRAL VALVE PROLAPSE WITH VARYING DEGREES OF MITRAL REGURGITATION
Abstract: The aim of the study is to correct the revealed disorders in patients with undifferentiated connective tissue dysplasia (UCTD) with primary mitral valve prolapse (MVP). 86 patients aged from 15 to 25 (19.5 ± 1.42) years were examined. ^he study showed that the magnesium preparation, especially in combination with L - arginine, improves the parameters of hemodynamics and heart function in patients with PMK.
Keywords: undifferentiated connective tissue dysplasia, mitral valve primary prolapse, treatment, L - arginine.
The problem of treating various clinical forms of UCTD is extremely complex and requires consideration of clinical manifestations of the pathology. Cases of generalized forms of UCTD that involve various organs and systems into the pathological process require an integrated therapeutic approach with the use of both nonmedicamentous and medicamentous methods of treatment. Pathogenetic drug therapy is of a substitutionary nature and it is carried out in several directions. First of all, it is stimulation of collagen formation, correction of glucosaminoglycans synthesis disorders, and a decrease in decomposition of these compounds. Stabilization of mineral metabolism, maintaining a sufficient level of free amino acids in the blood serum, and improving bioener-getic condition of the body should not be forgotten. [1].
It's been proven by many authors that the introduction of magnesium preparations in the course of treatment for patients with cardiovascular pathology contributes to restoration of the disturbed heart rhythm, as well as contributes to a significant decrease in the depth of cusp prolapse in the affected heart valve [2]. With Mg + 2 deficiency, transport-noncoding DNAs are resta-bilized (the number of dysfunctional RNA molecules increases), which is accompanied by a slowing down of synthesis rate of protein structures of cells with a relative predominance of the apoptosis process [3]. In connection with this, we used a magnesium preparation in the treatment of patients with congenital MVP, which
[5] provided a distinct positive dynamics of clinical and instrumental symptoms of UCTD manifestations. Another preparation used was L-arginine, providing for antihypoxic, membrane stabilizing, cytoprotective, an-tioxidant action.
The above listed facts stipulated the process of this study, which goal is correction of the revealed disorders in patients with undifferentiated connective tissue dys-plasia in primary mitral valve prolapse with various degrees of mitral regurgitation.
Materials and methods. 86 patients aged between 15 and 25 (19.5 ± 1.42) with signs of primary MVP were examined and diagnosed based on the classification by T. I. Kadurina [4]. The diagnosis and was later confirmed by EchoCG and ECG studies. Patients with UCTD and with mitral valve prolapse demonstrated significant reduction in serum magnesium and dysfunction of the endothelium, the severity of which depended on the degree of regurgitation. The patients were divided into 2 groups: group 'A' 45 patients with MVP, treated with a magnesium preparation in a daily dose of 3.0 (2 tablets 3 times a day for 10 days, then 1 tablet 3 times a day for 6 months) and group 'B', 41 patients with MVP, who were prescribed a 6-month course of preventive and therapeutic treatment with preparation of magnesium + L-arginine in a daily dose of 4.2 g, administered with 100 ml physiological solution for 7-10 days daily intravenously, with a subsequent 2 months interval. The course
was repeated three times. The efficacy was assessed based on clinical laboratory and instrumental studies.
The conducted studies showed high efficiency of the proposed treatment methods of UCTD with MVP. Thus, with use of magnesium preparation (group A), the frequency of patients' complaints of dyspnea decreased statistically significantly by 2.86 (P < 0.001) and 2.44 (P < 0.001) times, complaints of air shortage decreased significantly by 10 (P < 0.001) and 7.35 (P < 0.001) times, respectively to the degree of regurgitation. Despite this, 35 and 40.9% of patients retained complaints of mild dyspnea. Dyspnea of average severity, observed in these patients prior to treatment, turned into a light degree in some patients. Severe and moderate dyspnea, observed in these patients before treatment, remained as a mild degree of air deficiency in 10 and 13.6% of patients. The patients did not complain of headaches. The frequency of ECG disorders detection in patients of this group decreased by 4.5 (P < 0.001). As it can be clearly seen from the data presented, prescription of magnesium preparation had a positive effect, contributing to a significant decrease in the clinical manifestations of mitral valve prolapse.
Inclusion of L-arginine into the treatment scheme in addition to magnesium (group B) contributed to even more increase in the effectiveness of treatment. Thus, the frequency of dyspnea complaints decreased by 3 (P < 0.001) and 2.87 (P < 0.001) times, relative to pre-treatment values; by 1.05 and 1.18 (P < 0.05) times in comparison with the group of patients receiving only the magnesium preparation, respectively to the degree of regurgitation. At the same time, the average degree of dyspnea was not detected, but 33.3 and 34.8% of patients complained of mild dyspnoea. In this group, after long-term treatment, patients did not complain about air deficiency, whereas in Group A these complaints remained in 10 and 15.6% ofpatients.Just like in Group A, patients in Group B did not complain of headaches after treatment. The changes in ECG, previously observed in patients with UCTD, were not detected after treatment with both preparations, whereas in the group of patients, which received only magnesium preparation, these changes remained in 10 and 18.2% of those treated.
The data obtained indicate high efficiency of the combined use of magnesium and L-arginine for treatment of UCTD with MVP of varying severity. In our
opinion, this is due to a significant improvement in the synthesis of collagen and elastin in fibroblasts under the influence of magnesium ions.
It should be noted that certain changes in the parameters of Doppler echography were noted in patients with UCTD and the presence of MVP, the severity of which increased depending on the degree of regurgitation. Pharmacotherapy of MVP in patients using magnesium preparation showed positive dynamics within 3 months. Thus, patients of group A showed an improvement in the basic indicators characterizing the rhythm and contractile heart activity. This was manifested by a decrease in the parameters of EDD, ESD, systolic and diastolic blood pressure, the number of cardiac contractions on the background of an increase in the parameters of the ejection fraction, cardiac systolic output, MBV. However, these changes were statistically insignificant, especially in patients with second degree of regurgitation.
More pronounced changes in echogeometry of the heart were detected with a longer application. After a 6-month course of treatment with the above medication, EchoCG studies showed that EDD and ESD decreased by 10% (P > 0.05) and 16.8% (P < 0 .01) with 1-st degree of regurgitation, by 10.3% (P < 0.05), and 16.5% (P < 0.01) with the 2nd degree of regurgitation. The values of cardiac systolic output also significantly decreased by 11.9 (P < 0.05) and 9.8% with respect to the initial parameters. The thickness of the posterior wall of the left ventricle tended to decrease, while the values of the intermembrane septum changed significantly: a decrease of 14 (P < 0.05) and 15% (P < 0.05), respectively to MVP regurgitation.
Low values of ejection fraction increased by 11.6 and 16.9% (P < 0.05) relative to the initial parameters, respectively. In addition, there was observed a veracious decrease in heart rate, while the values of SBP and DBP only had a tendency to increase.
A more pronounced clinical efficacy of the 'magnesium' preparation in UCTD patients with MVP was noted after 6 months of treatment. It can be assumed that the lack of sufficiently complete clinical efficacy in patients with UCTD and MVP was associated with the different action of the magnesium preparation in patients with varying degrees of valve regurgitation. Magnesium preparation had a more pronounced pharmacological effect in patients with more pronounced disorders.
Consequently, our observations show that only with prolonged use. Clinical efficacy is increased depending on individually selected doses of the preparation; the dose of 'Magnesium Preparation' 1 tablet 3 times a day, i.e. 3g / day is enough to improve the myocardial contractility in 6 months, while the basic mechanism of MVP compensation does not suffer.
The patients of B group received L-arginine together with a preparation of magnesium. In this group of patients, we observed changes that are more pronounced in cardiac hemodynamics. Pharmacotherapy of MVP in patients with the use of the magnesium preparation + L-arginine for 3 months showed a positive trend. Thus, in patients of group A, there was a decrease in the studied parameters of cardiac hemodynamics, systolic and diastolic blood pressure, and the number of heartbeats against the background of an increase in the parameters of cardiac systolic output. However, these changes were statistically insignificant, especially in patients with a second degree of regurgitation.
More pronounced changes in the echogeometry of the heart were detected with longer application. After a 6-month course of treatment with this preparation, EchoCG studies showed that EDD and ESD decreased by 20% (P > 0.05) and 29.1% (P < 0.01) with the first degree of regurgitation, by 21.4% (P < 0.05), and 32.5% (P < 0.01) with the second degree of regurgitation. The values of cardiac systolic output also significantly decreased by 19 and 17.6% with respect to the initial parameters. The thickness of posterior wall of the left ventricle decreased by 9.2 and 19.6% (P < 0.05), while the values ofthe intermembrane septum changed significantly by 21.9 (P < 0.05) and 18.5% (P < 0.05), respectively to MVP regurgitation. Low values of ejection fraction increased by 10.3 and 20.6% (P < 0.05) relative to the initial parameters, respectively. Along with this, there was observed a veracious decrease in heart rate, while the values ofSBP and DBP only had a tendency to increase. A more pronounced clinical efficacy of the proposed therapy in UCTD patients with MVP was noted after 6 months of treatment. At the same time, a more complete clinical efficacy, observed in patients with UCTD and MVP, was associated with different effects ofboth preparations in patients with varying degrees ofregurgitation.
The performance analysis of flow-dependent vasodilatation in the compared groups of individuals with MVP and varying degrees of blood flow regurgitation during the 6-month prophylactic treatment showed that
the magnesium preparation had no significant effect on the diameter of brachial artery before and after the test in patients with 1st degree MVP. The test revealed only a tendency to an increase in brachial artery diameter. In this regard, the increase in the diameter after the test in treated patients with 1-st degree MVP was statistically significant: by 1.53 (P < 0.01) with respect to the values before treatment, and got close to that of practically healthy individuals. However, the values of MSPPA, which had only a tendency to increase before the treatment, statistically significantly increased after the test by 1.53 (P < 0.01) times relative to the initial values, which led to an increase in the resistance index by 1.5 (P < 0.01) times, with respect to values before treatment.
At the same time, in patients with II degree MVP, who received the magnesium preparation for 6 months, the values of DBA before and after the test did not change significantly, and the gain statistically significantly increased by 1.27 (P <0.05) times. In this case, both the values of MSPPA before and after the test and the resistance index did not change with respect to the initial values. All the studied indicators of this subgroup of patients were statistically insignificantly different from the values of practically healthy individuals.
In patients of group B, treated with magnesium preparation + L-arginine, positive dynamics was observed in patients with MVP 1st degree of regurgitation. The values of DBA before and after the test tended to increase, the growth statistically significantly increased by 1.62 (P < 0.001) times relative to values before treatment. However, this figure remained significantly below the normative values. The MSPPA index before the treatment had only a tendency to increase, while its values after the test significantly increased by 1.4 (P < 0.05) times, which led to an increase in the resistance index by 1.39 (P < 0.05) times compared to before treatment. All the studied parameters were statistically significantly different from the values of practically healthy individuals.
In patients with the 2nd degree of mitral valve regurgitation, who received magnesium + L-arginine, the values of flow-dependent dilatation did not differ significantly from the initial parameters and were significantly different from those of practically healthy individuals. As can be seen from the data presented, the use of the magnesium preparation alone and in combination with L-argi-nine had a positive effect on vascular wall parameters in
patients with the first degree of regurgitation, whereas in patients with the 2nd degree of regurgitation the effectiveness of treatment was weak.
Our observations show that magnesium preparation in combination with L-arginine has a more pronounced pharmacological effect with prolonged use. Apparently, this is due to potentiation of magnesium preparation under the influence of L-arginine. However, it should be noted that L-arginine itself corrects the observed endo-thelial dysfunction.
Thus, the results of the studies showed that magnesium preparation, especially in combination with L-ar-ginine, improves the parameters of hemodynamics and heart function in patients with MVP, which pathogeneti-cally substantiates its prescription as adequate treatment for prophylactics and preventive therapy for patients with UCTD and MVP. However, their effectiveness in terms of correcting endothelium-dependent dilatation was noted only in patients with the first degree of regurgitation.
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