Primary Mitral Valve Prolapse Research Articles

MİTRAL KAPAK PROLAPSUSU OLAN ÇOCUKLARDA KARDİYAK OTONOMİK DİSFONKSİYONUN VE ARİTMİ RİSKİNİN DEĞERLENDİRİLMESİ

Objective: The occurrence of symptoms in patients with mitral valve prolapse (MVP) is linked to autonomic dysfunction and neuroendocrine causes rather than progressive mitral valve insufficiency. The goal was to assess the risk of autonomic dysfunction and arrhythmia in patients with MVP.
 Methods: The study included 63 patients with primary MVP and a control group of 64 children of similar age and gender. Following a physical examination, all patients' histories were taken, and 12-lead ECGs, autonomic function tests, echocardiography, and 24-hour Holter rhythm studies were performed.
 Results: The patient group had a higher mean resting heart rate than the control group. Orthostatic hypotension was found in 8 patients (12.6%) and 4 children (6.2%) in the control group. When compared to the control group, patients with MVP had higher QTc dispersion, frontal QRS-T angle, Tp-e interval, and Tp-e/QTc ratio. There was no significant difference between the two groups in terms of conventional measurements of heart rate variability in the Holter ECG, as well as no significant difference in HRDC.
 Conclusion: Although cases with pathological findings in the initial ECG were excluded from our study, we believe that the high frontal QRS-T angle observed in MVP patients is a novel and significant finding. Furthermore, it has been discovered that HRDC, a new and understudied parameter in children, does not show a significant difference in patients with MVP.

Mitral valve prolapse: do we correctly understand the problem in a particular child?

The lecture is devoted to the role of mitral valve prolapse in children and adolescents, in the population and in the formation of health. Particular attention is paid to the mechanisms of its formation, the evolution of the mitral valve prolapse criteria. The reasons for its overdiagnosis,risk factors, as well asthe high frequency of complications are explained. The interrelation of this pathology with connective tissue dysplasias and the inappropriateness of classifying the defect as a group of minor heart anomalies are emphasized. Primary mitral valve prolapse is an independent disease. There is no proven basis to consider it a marker or «affiliation” of systemic connective tissue dysfunction. An algorithm of modern treatment and prevention of mitral valve prolapse for modern pediatric practice is presented.

The state of response of autonomic nervous system in children with mitral valve prolapse

The article presents summarized materials on connective tissue dysplasia of the heart, primary mitral valve prolapse, dysfunction of the autonomic system. Aim of research: to estimate the condition of autonomic nervous system in children with primary mitral valve prolapse. We examined 106 children with mitral valve prolapse aged from 13 to 17 years old on the clinical base of city hospital “Center of mother and child” in Vinnitsya. Research included time and frequency domain (evaluation with cardiointervalography. Final results were compared with the control group records. The results showed no statistical significance among time domain parameters in the main group of children. All these indices displayed tendency to sympathetic and parasympathetic autonomic nervous system tonus increase in boys. However, sympathicotonia tendency was noted in girls only. Frequency domain parameters showed similar results, compared with the previous. Nevertheless, very low frequency parameters had statistically significant difference in both subgroups of patience with mitral valve prolapse, including males (3205.8±190.9 against 1717±154, р<0.05) and females (3280±220.1 against 1433±811, р<0.05). There were no statistically significant difference among other frequency domain parameters. Conclusions: we estimated that children with mitral valve prolapse have imbalanced autonomic homeostasis manifested by tone disturbances of both autonomic vegetative system branches with sympathetic predominance. Patients with primary mitral valve prolapse generally have increased sympathetic tone - both boys and girls - according to spectral analysis of heart rate variability indices, heart rate oscillation power of a very low frequency in particular (p<0.05). In children with mitral valve prolapse, the tone of parasympathetic nervous system is generally normal; there is a tendency to its increase in boys and decrease in girls. These children should be under close medical supervision by pediatricians and cardiologists.

Mitral annular disjunction in patients with primary severe mitral regurgitation and mitral valve prolapse.

Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus which is often associated with mitral leaflet prolapse. However, few reports have described mitral annular disjunction in mitral valve prolapse (MVP). This study aimed to investigate the characteristics of mitral annular disjunction in patients with severe mitral regurgitation (MR) caused by MVP. We reviewed 185 consecutive patients with severe MR caused by fibroelastic deficiency (FED) and Barlow's syndrome from March 2009 to December 2010. The upper limit of the disjunction was defined at the level of the posterior scallop's insertion into the left atrial wall, whereas the lower limit was defined at the level of the left atrium's connection to the ventricular myocardium. The distance between the two levels was called mitral annular disjunction. Prolapse sites in FED patients were categorized into anterior leaflet, posterior leaflet, and commissure groups. Patients with a disjunction distance of ≥2mm were diagnosed with mitral annular disjunction. Annular disjunction was found in 45 patients (24%). Among them, the most common site of prolapse was the posterior leaflet (n=35, 77.8%). During a median follow-up of 20.3years, arrhythmic events and sudden death occurred in seven patients (3.8%). Mitral annular disjunction was detected in 24% of patients with severe MR and in 90% of the patients with Barlow's syndrome. There were significant differences at its sites of prolapse in FED patients. The presence and site of prolapse with mitral annular disjunction should be actively determined in FED patients.

Диспластический фенотип пациентов с первичным пролапсом митрального клапана (обзор литературы)

Диспластический фенотип пациентов с первичным пролапсом митрального клапана (обзор литературы)

Features of rheoencephalography in children with primary mitral valve prolapse

Annotation. Mitral valve prolapse (MVP), as a manifestation of connective tissue dysplasia, is of great interest in the field of medicine. It occupies an important place in the structure of diseases of the cardiovascular system, which is mainly due to its high incidence and possible complications. MVP is detected in almost 2–3% of the population. In addition, this pathology with a genetic predisposition is a manifestation of a connective tissue defect and is rare in newborns and at an early age, which characterizes it as a progressive disease. At the moment, the features of cerebral hemodynamics in children with MVP are not well understood. The aim of our study was to study cerebral hemodynamics in children with primary mitral valve prolapse using quantitative indicators of rheoencephalography (REG). The study included patients with primary MVP. Under our supervision, there were 106 children aged 13 to 17 years. The control group included 23 healthy children at the same age. All children underwent a REG with quantitative indicators. In children with MVP, there is a variability in the results of REG in the cerebral hemispheres. Vascular elasticity is significantly reduced due to anacrot time increase (p<0.001), which, in fact, is characteristic of the hypertonic type of blood flow (57.5%). It can be argued that in children there is a hypovolemic type of blood flow in the form of a decrease in the rheographic index relative to the control group (p<0.05). There is a tendency to vascular tone tension of all calibers according to the absence of statistically significant deviations of the corresponding indicators (dictrotic index and the ratio of the duration of the ascending phase to the duration of the entire pulse wave). The same picture is observed with venous blood flow, according to the values of the dystolic index in the carotid artery basin. In the basin of the vertebral artery there is a tendency to increase the tone of small vessels and venous vessels. Thus, in children with mitral valve prolapse, cerebral blood flow changes in the form of hypovolemia in the carotid artery basin and normovolemia in the vertebral artery basin according to REG parameters; in this group of children with MVP, there is a tendency to tension in the tone of blood vessels of all calibers according to the absence of statistically significant deviations of the corresponding indicators (dictrotic index and the ratio of the duration of the ascending phase to the duration of the entire pulse wave). Also, patients with MVP should be constantly monitored by narrow specialists (cardiologists, neurologists) for timely and adequate recovery.

The activity of transforming growth factor-β in young age with marfanoid habitus

According to contemporary views, hereditary connective tissue disorders divided classified Marfan syndrome, Loeys-Dietz’s, Ehlers-Danlos syndrome, the primary mitral valve prolapse. It is known that the fibrillinopaty, which include the Marfan syndrome and Loeys-Dietz’s is characterized by activation of TGF-β signaling pathway. With high le vels of TGF-β attributed most of these clinical manifestations these diseases – aneurysm of the aorta, arahnodaktylya, duralectasy. Assessment of the activity of TGF-β in persons with marfanoid habitus has not previously been studied.
 Materials and methods. As part of this work, surveyed 70 people: 61 patients young age (median age of 20.1 ± 2.1 years), among which 36 boys and 25 girls and 9 men with verified diagnosis Marfan syndrome (median age 27.9 ± 9.3 years). All survey performed Echocardiography with a targeted search of small anomalies of heart.
 Results. Correlation analysis showed a direct and reliable connection between arahnodaktylya and concentration of TGF-β1 in serum (r = 0.4, p = 0.05). For young people with signs of marfanoid habitus are characterized by reliably a higher concentration in the serum of both isoforms of TGF-β. Excess of threshold levels of TGF-β1 revealed at 20% of the core group and not found at all in the control (p < 0.05). Among persons with exceedances of threshold values for at least one faction of the TGF-β patients with signs of marfanoid habitus met almost three times more often than in the group with normal values of TGF-β (p = 0.01, χ2 = 5.58). In the group of persons with marfanoid habitus and increases TGF-β are detected more frequently such as atrial septal aneurysm, false chord left ventricle papillary muscles, incremental, deflection of shutters of the mitral valve in 1-2 mm, asymmetry tricuspid aortic valve.

Indicators of vegetative homeostasis in children with mitral valve prolapse before and after treatment

For children with mitral valve prolapse (MVP) characterized by disorders of vegetative homeostasis, especially pronounced effect on the body sympathetic link of the autonomic nervous system. In the medical literature, the question of correction of vegetative tone in children with primary MVP is now open. The purpose of the study was to study the parameters of vegetative homeostasis in children with mitral valve prolapse before and after treatment. 66 children with primary and primary MVP stage I and II at the age of 13–17 years were examined. The control group consisted of 23 practically healthy children. The evaluation of vegetative homeostasis was performed using a clinorostatic test and cardiointervalography, followed by an analysis of the parameters and parameters of the heart rate variability spectral analysis. To restore vegetative homeostasis to patients with PMC, an existing treatment regimen with our correction was prescribed. Namely, we added therapies levocarnitine and magnesium. According to the data obtained from the CP, we found that treatment led to the normalization of vegetative maintenance of the organism, mainly in the form of a decrease in the hypersympathicotonic tonic type after treatment, along with the baseline (p<0.05). Consequently, the proposed treatment scheme with the use of levocarnitine and magnesium, positively affects the autonomic system in children with primary MVP, reducing its dysfunction.

Cardiac arrhythmias and predictors in patients of young age with marfanoid habitus

Cardiac arrhythmias are frequent manifestations of hereditary connective tissue disorders (HCTD). Such HCTD as Marfan syndrome (MS), the primary mitral valve prolapse are characterized by frequent supraventricular and ventricular extrasystoles, prolonged PQ and QT interval, reduced heart rate variability and frequent findings of other predictors of heart arrhythmias. Cardiac arrhythmias as well as their predictors in patients of young age with marfanoid habitus (MH) were not previously evaluated.
 Materials and methods. A total number of 238 patients of young age were examined. All patients received phenotypic and anthropometric screening and Holter ECG. Cardiac arrhythmias, duration of QT interval (QTc), QT dispersion (QTd), heart rate variability and heart rate turbulence were estimated.
 Results for young people with MH as compared with the control group are characterized by frequent detection of paired (42.6% vs 9.7%, p= 0.00001), group (17.0% vs 4.2%, p = 0.01) supraventricular extrasystoles, ventricular extrasystoles in pathological quantity (10.6% vs 1.4%, p = 0.02). Pathological value of heart rate turbulence is detected significantly more frequently in individuals with MH. During evaluation of variability a significant decrease in all spectral (HF, LF, VLF), as well as most statistical (SDNN, pNN50) indicators was revealed. Patients with MH are characterized by prolonged QT interval (QTc threshold in 480 ms overcomes 21% of boys with MH, p = 0.00001) and increase the variance of the QT interval (threshold of 50 ms overcomes 37.5% of girls with MH, p = 0.0004).

Early Impairment Left Ventricular Mechanics in Children With Mitral Valve Prolapse

Early impairment of left ventricular (LV) function has been reported in some inherited connective tissue diseases such as Marfan syndrome or rheumatic heart disease in pediatric patients. However, there is no study about cardiac strain in pediatric patients with primary mitral valve prolapse (MVP). The aim of this study was to evaluate the LV functions in pediatric patients with primary MVP, mild or moderate mitral regurgitation (MR), and normal LV ejection fraction. The study group included 72 consecutive patients (40 female, mean age: 13.1 ± 5.2 with primary MVP who had mild or moderate MR, and normal systolic function (LV ejection fraction ≥60%) were compared with 40 healthy children using conventional echocardiography, tissue Doppler imaging, and 2-dimensional speckle tracking echocardiography. Patients were divided into subgroups according to the MR severity: mild (n:34), and moderate (n:38) and leaflet thickness: classical (n: 40), and nonclassical (n: 32). The children with MR had significantly lower values for global early diastolic strain rate ([SRe] patients: 1.40 ± 0.25 vs controls: 1.62 ± 0.54; p = 0.001), and E/SRe (patients: 72.7 ± 5.6 vs controls: 62.1 ± 4.9; p <0.04) when compared with the control group. In subgroup analysis, SRe (mild: 1.49 ± 0.38 vs moderate: 1.32 ± 0.31; p <0.001) was lower in MVP patients with moderate MR compared to mild MR, and E/SRe (mild: 69.4 ± 5.1 vs moderate: 75.1 ± 6.4; p <0.001) value was higher in MVP patients with moderate MR compared to mild MR. Diatolic strain parameters, SRe, and E/SRe are more sensitive markers of early subtle myocardial injury in pediatric patients with primary MVP.

DIAGNOSTIC SIGNIFICANCE OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN PATIENTS WITH PRIMARY MITRAL VALVE PROLAPSE

Aim. To evaluate diagnostic significance of the type A vascular endothelial growth factor (VEGF-A) and its receptors type 1 and 2 (VEGF-R1 and VEGF-R2) in primary mitral valve prolapse (MVP) patients. Material and methods. Totally, 83 MVP patients studied: 61 males, 22 females; mean age 21,93±4,22 y. o. The signs of systemic inflammation were assessed, as the grade of connective tissue involvement. Immune enzyme analysis was done for serum levels of VEGF-А, VEGF-R1 and VEGF-R2 (“Bender MedSystems GmbH”,Austria). Controls included 20 healthy volunteers — 14 males, 6 females, mean age 21,10±0,55 y. o. with no MVP and any other dysplastic features. Results. In the MVP group, the decreased levels of circulating VEGF-R1 were found, as the increase of cases number of high (42,17%) and low (32,53%) concentration of VEGF-А. In low levels of VEGF-A and VEGF-A/ VEGF-R1 prevalence of grade II mitral regurgitation increases 5,1 times comparing to the group of retained balance of VEGF-A and VEGF-R1 — 95% confidence interval (CI) 1,25-20,88, and the prevalence of clinically significant cardiac rhythm and conduction disorders increases 5,25 times in comparison to the cases with elevated VEGF-A and VEGF-R1 — 95% CI 1,33-20,76 and 4,09 times — comparing MVP patients with retained balance of VEGF-A and VEGF-R1 — 95% CI 1,18-14,17. Conclusion. In primary MVP patients, regardless clinical phenotype of monogenic hereditary syndromes, the heterogeneity of deviation and regulation of VEGF has been established. Highest number of II grade mitral regurgitation, significant rhythm disorders was found in the group with low VEGF-A and VEGF-A/VEGF-R1, that might be implemented as optimized risk stratification in heterogenic MVP patients population.

P210Long- term outcome of primary mitral valve prolapse: results from a population of 250 patients referred to a tertiary cardiovascular center.

Outcome of Mitral Valve Prolapse (MVP) was controversial for long time. Many studies reported great differences in the incidence of cardiovascular events due, above all, to heterogeneous and small studied populations. Most of theme were also published to late '80 of the last century till early '00. To make a contemporary survey on the incidence of cardiovascular events in a selected population of patients affected by primary MVP referred to a tertiary cardiovascular center for the medical and surgical care of valvular heart disease. We reviewed our MVP database; patients with at least 2 cardiologic evaluations inclusive of echocardiographic examination and at least 6 months follow up were enrolled. A total of 250 patients (126 F) were selected. Their mean age was 52.1 years (ranging from 13 to 88 yo). The average follow-up time was 100 months (8,33 yrs). At the first medical and echocardiographic examination 8 patients (3,2%) had no mitral regurgitation (MR), 104 (41.6%) have a trace/mild MR, 93 (37,2%) a moderate MR and 46 (18,4%) a severe MR. They were widely asymptomatic (NYHA I 205-82%, NYHA II 44-17.60%, NYHA III 1- 0.40%). Most of theme presented a bileaflet (140-55.8%) or a posterior MVP (94 - 37.6%); an isolated anterior MVP was rare (16 - 6,4%). Flail leaflet was present in 8 (3,2%) and 25 (10%) had a chordal rupture. Respectively 165 (65,6%) and 115 (46,1%) patients had thick and redundant leaflets. Mean antero-posterior mitral annulus diameter was 37 mm. During the follow up 7 patients died of non-cardiac cause and 5 (2%) of suspected cardiac cause (2 because of acute coronary syndrome and 3 died suddenly). MR progresses in 43 (17,2%) patients and finally we observed 81 (32,4%) moderate/severe and severe MR. 12 new chordal rupture occurred during the follow up in most cases concerning mitral chordae linked to posterior mitral leaflet (10 cases-83,3%). The worsening of MR provoked an evolution of the clinical condition of 48 patients (19.2%) which developed Dyspnea On Excertion (DOE) with 42 new NYHA II and 6 new NYHA III. At the end of the follow up the amount of patients symptomatic for DOE was 93 (37.2% vs 18% at the initial evaluation). A total of 45 patients (18%) underwent mitral valve surgery. 40 needed in-hospital treatment in most cases due to the development of atrial fibrillation (19 -7.6%) or heart failure ( 8- 3,2%). Endocarditis occurred in 4 patients (1.6%) and cerebrovascular accidents/cardioembolic event in 6 (2.4%). The overall cardiovascular event rate was 4,33/100 patients-year, significantly higher than reported in community based studies. The prognosis of a MVP population referred to a tertiary cardiovascular center is not benign. The most frequent complications are progression of MR and MV surgery. Sudden death is also more frequent than in general population. More studies are needed to identify what patients with MVP are at risk for it.

QT dispersion and ventricular arrhythmias in children with primary mitral valve prolapse

To investigate ventricular arrhythmias in children with primary mitral valve prolapse and to evaluate its relation with QT length, QT dispersion, autonomic function tests and heart rate variability measurements. Fourty two children with mitral valve prolapse and 32 healthy children were enrolled into the study. Twelve-lead electrocardiograms, autonomic function tests, echocardiography and 24-hour rhythm Holter tests were performed. Electrocardiograms were magnified digitally. The QT length was corrected according to heart rate. The patients were grouped according to the number of premature ventricular contractions and presence of complex ventricular arhythmia in the 24-hour rhythm Holter monitor test. Heart rate variability measurements were calculated automatically from the 24-hour rhythm Holter monitor test. Orthostatic hypotension and resting heart rate were used as autonomic function tests. The mean age was 13.9±3.3 years in the patient group and 14.6±3.1 years in the control group (p>0.05). Thirty four of the patients (81%) were female and eight (19%) were male. Twenty five of the control subjects (78%) were female and seven (22%) were male. The QT dispersion and heart rate corrected QT interval were found to be significantly increased in the children with primary mitral valve prolapse when compared with the control group (56±16 ms vs. 43±11 ms, p=0.001; 426±25 ms vs. 407±26 ms, p=0.002, respectively). In 24-hour rhythm Holter monitor tests, ventricular arrhythmias were found in 21 out of 42 patients (50%) and 6 out of 32 control subjects (18.8%) (p=0.006). QT dispersion was found to be significantly increased in patients with premature ventricular contractions ≥ 10/day and/or complex ventricular arrhythmias compared to the control group without ventricular premature beats (p=0.002). There was no significant difference in autonomic function tests and heart rate variability measurements between the patient and control groups. The noted increase in QT dispersion may be a useful indicator for the clinician in the evaluation of impending ventricular arrhythmias in children with primary mitral valve prolapse.

The specifics of adhesion function of endothelium in various clinical variants of primary mitral valve prolapse

Aim . To assess the condition of adhesion function of endothelium in various clinical variants of primary mitral valve prolapse (MVP). Material and methods. Totally, 91 patient studied with primary MVP at the age 21 (19-24) y. First grade mitral regurgitation was found in 45,1% and II — in 54,9% patients. MVP was solitary variant (6,6%) and comorbid with 1-3 minor anomalies of the heart (93,4%). Doppler-echocardiography was done on Vivid07 equipment (Israel). The grade of systemic involvement of connective tissue was 2 (1,5-4,0) points. Controls were 10 healthy persons, matched by age, sex, smoking, body mass index. By the immune enzyme method we checked plasmatic concentrations of L-, E-, Р-selectins, ICAM-1, VCAM-1, PECAM-1 (Bender MedSystems GmbH, Austria). Findings are presented as mediana (25-75 percentiles). Results . In MVP patients the levels of Е-selectin — 43,0 (33,7-54,8) ng/ mL, ICAM-1 — 669,9 (546,4-883,3) ng/mL and VCAM-1 — 925,0 (707,5- 1215,0) ng/mL, were significantly higher, and the level of РЕСАМ-1 — 49,8 (40,4-63,2) ng/mL, in opposite, lower than in control group. L- and P-selectins levels in MVP group were measured as relevant to controls values (p>0,05). In regurgitation cases of II degree, the level of E-selectin and ICAM-1 were maximal (p<0,05). Values of VCAM-1 in MVP patients independently from degree of regurgitation were significantly higher than controls values. There was moderate direst relation of the quantity of minor heart anomalies and level of ICAM-1 (rs=+0,30, р<0,05). In MVP group with increased E-selectin significantly higher was aorta diameter at the level of Valsalva sinuses — 2,5 (2,3-2,7) cm, than in PMV without increased E-selectin level — 2,3 (2,2-2,5) cm (р<0,05). Conclusion . In patients with primary MVP there is an increase of circulating concentrations of E-selectin, ICAM-1, VCAM-1, that represents the level of adhesion, and witnesses about subclinical endothelial dysfunction. For screening evaluation of severity of adhesion disorders of endothelium in MVP it is important to take into account its hemodynamic significance, multiple minor heart anomalies and data on aorta diameter on the level of Valsalva sinuses.

Massive Hemoptysis due to Acute Mitral Regurgitation with Sporadic Primary Mitral Valve Prolapse

Massive Hemoptysis due to Acute Mitral Regurgitation with Sporadic Primary Mitral Valve Prolapse

HEREDITARY CONNECTIVE TISSUE DISORDERS: NOMENCLATURE AND DIAGNOSTIC ALGORITHM

Hereditary connective tissue disorders (HCTDs) are a genetically and clinically diverse group of diseases, which encompasses common congenital disorders of fibrous connective tissue structures. Out of the whole variety of the clinical manifestations of NCTDs, only differentiated monogenic syndromes with the agreed guidelines for their diagnosis have been long the focus of the medical community’s attention. Many unclassified forms of the pathology (dysplasia phenotypes) have been disregarded while assessing a person’s prognosis and defining treatment policy. With no clear definition of NCTDs or their approved diagnostic algorithm, it is difficult to study their real prevalence in the population, to compare literature data, and to constructively discuss various scientific and practical aspects of this disease. Efforts to systematize individual clinical types of NCTD and to formulate their diagnostic criteria are set forth in the All-Russian Research Society Expert Committee national guidelines approved in 2009 and revised in 2012. The paper gives current views on the nomenclature of NCTDs, considers diagnostic criteria for both classified monogenic syndromes (Marfan's syndrome, Ehlers–Danlos' syndrome, MASS phenotype, primary mitral valve prolapse, joint hypermobility syndrome) and unclassified dysplasia phenotypes (MASS-like phenotype, marfanoid appearance, Ehlers–Danlos-like phenotype, benign joint hypermobility syndrome, unclassified phenotype). The above abnormalities are presented as a continuous list drawn up in the decreasing order of the degree of their clinical manifestations and prognostic value (the phenotypic continuum described by M.J. Glesby and R.E. Pyentz): from monogenic syndromes through dysplasia phenotypes to an unclassified phenotype. Emphasis is laid on the clinical NCTD identification difficulties associated with the lack of specificity of external and visceral markers of connective tissue asthenia and with the certain conventionality of NCTD diagnostic criteria. Debatable problems in the diagnosis and interpretation of the clinical significance of individual NCTDs are represented.

Role of heritable connective tissue diseases phenotypes in assessing the risk for internal diseases

Aim. To identify the prevalence of main phenotypes of polygenic heritable connective tissue diseases in patients with internal diseases and to assess the prevalence of different internal diseases in such patients. Methods. The study involved 600 patients (254 males, 346 females) aged 18 to 64 years. Average age of males was 52±3.8 years, females - 47±2.2 years. Patients were examined to reveal the signs of different phenotypes of heritable connective tissue diseases in patients with internal diseases, as well as the severity of connective tissue diseases, and possibilities for it screening using the wrist and thumb hypermobility tests. Results. Signs of heritable connective tissue diseases were revealed in 147 (24.5%) patients with internal diseases. In females, those signs were observed in 104 (30.0%) cases, of which 44 (42.3%) were graded as mild, 35 (33.7%) - moderate, 25 (24.0%) - severe. In males, signs of heritable connective tissue diseases were revealed in 43 cases (16.9%), including mild - 17 (39.5%), moderate - 14 (32.5%) and severe - 12 (28.0%). Ehlers-like phenotype was the most common (52.0%), Marfan-like phenotype was observed in 14.0% of cases, primary mitral valve prolapse was diagnosed in 7.0% of patients, unclassifiable phenotype was observed in 11.0% of cases. Joint hypermobility syndrome was revealed in 31.0% of patients, presenting both as specific phenotypes (Marfan-like, Ehlers-like) and as a self-phenotype (31.9% of all the patients with heritable connective tissue diseases phenotype). Benign joint hypermobility was observed in 6.1% of cases. Symptoms of heritable connective tissue diseases were more frequent in patients with gastrointestinal and musculoskeletal diseases. Conclusion. The most common phenotype of heritable connective tissue diseases is Ehlers-like with skin, bone and systemic manifestations. Presence of heritable connective tissue diseases was most commonly associated with gastrointestinal and musculoskeletal diseases.

SYSTEMIC INVOLVEMENT OF CONNECTIVE TISSUE AND THE HEART AS IMPORTANT CHARACTERISTICS OF PRIMARY MITRAL VALVE PROLAPSE

Aim. To evaluate systemic involvement of connective tissue (SICT) in young adults with mitral valve prolapse (MVP) without significant mitral regurgitation (MR). Material and methods. We studied 78 asymptomatic young subjects (mean age 19,7±1,6, 72% male) with MVP in comparison with 80 sex- and age-matched healthy subjects. We performed phenotypic examination of MVP patients and control group subjects, and echocardiographic study to identify the minor heart anomalies. Longitudinal strain and strain rate (SR) were determined using spackle tracking (Vivid 7 Dimension GE, EchoPAC’08). Results. We identified two clusters of patients with MVP. In the first cluster (17 subjects, 28% of the MVP group) a significant reduction of longitudinal systolic strain observed comparing to the control group and the second cluster (61 subjects, 72%). Global strain in the second cluster did not differ significantly from the control group. Echocardiographic study showed nonsignificant increase in the average number of SICT points in the first cluster and highly significant increase of the minor heart anomalies’ number in this group of patients. Conclusion. Myocardial deformation assessment allowed to identify the signs of cardiomyopathy in quarter of young asymptomatic patients with MVP. Increasing number of minor heart anomalies in the group with primary MVP and cardiomyopathy allows considering other valve prolapses, dilatation of major vessels, basal and thick LV chords as features of the SICT in primary MVP. A great number of minor heart anomalies in primary MVP may indicate a change in the heart extracellular matrix that can cause the development of cardiomyopathy in primary MVP.

Systemic connective tissue involvement and cardiac involvement: the 2010 revised Gent nosology in the Marfan syndrome diagnostics

The author presents his view on the problem of Marfan syndrome-related hereditary connective tissue disorders, in particular, primary mitral valve prolapse and Marfanoid habitus, as the most prevalent manifestations. The changes in the assessment of external and visceral manifestations of Marfan syndrome, according to the originalGentnosology and its 2010 revision, are discussed. The importance of the evaluation of systemic connective tissue involvement, with the systemic score calculation and cardiac extracellular matrix assessment, is emphasised. The author presents the evidence justifying the need for a wider use of the cardiac involvement concept, in order to assess the severity of structural and functional disturbances of cardiac extracellular matrix in patients with primary mitral valve prolapse and Marfanoid habitus. The cardiac involvement assessment should be based on the systemic score, minor cardiac criteria, the number and type of minor cardiac abnormalities, the results of clinical examination, and the serum levels of transforming growth factors (TGF)

Evidence of a Vicious Cycle in Mitral Regurgitation With Prolapse

In patients with mitral valve prolapse, nonprolapsed leaflets are often apically tented. We hypothesized that secondary left ventricular dilatation attributed to primary mitral regurgitation (MR) causes papillary muscle (PM) displacement, resulting in this leaflet tenting/tethering, and that secondary tethering further exacerbates malcoaptation and contributes to MR severity. Three-dimensional transesophageal echocardiography was performed in 25 patients with posterior mitral leaflet prolapse with an intact anterior mitral leaflet (AML) and 20 controls. From 3D zoom data sets, 11 equidistant antero-posterior cut planes of the mitral valve at midsystole were obtained. In each plane, tenting area of nonprolapsed leaflet and prolapse area of prolapsed leaflet were measured. Prolapse/tenting volume of each region was obtained as the product of interslice distance and the prolapse/tenting area. AML tenting volume and whole leaflet prolapse/tenting volume were then obtained. The PM tethering distance between PM tips and anterior mitral annulus was measured from 3D full-volume data sets. The severity of MR was quantified by vena contracta area extracted from color 3D transesophageal echocardiography data sets. AML tenting volume was significantly larger in patients with posterior mitral leaflet prolapse compared with that in controls (1.2 ± 0.5 versus 0.6 ± 0.2 mL/m(2); P<0.001). Multivariate regression analysis identified independent contribution to AML tenting volume from an increase in PM tethering distance. Multivariate regression analysis identified independent contributions to MR severity (vena contracta area) from both whole leaflet tenting volume (r=0.44; P<0.05) and prolapse volume (r=0.44; P<0.05). AML tenting volume decreased along with left ventricular volume and PM tethering distance postrepair (n=8; P<0.01). These results suggest that primary mitral valve prolapse with MR causes secondary mitral leaflet tethering with PM displacement by left ventricular dilatation, which further exacerbates valve leakage, constituting a vicious cycle that would suggest a pathophysiologic rationale for early surgical repair.