Aim To evaluate the effect of mitral valve (MV) repair and replacement on the incidence of ventricular arrhythmias (VA) and to identify risk factors for the persistence of VA in patients with MV prolapse and severe mitral regurgitation (MR) during a mid-term follow-up. Material and methods A single-site observational, prospective study successively enrolled 30 patients (mean age, 55.2±9.9 years, 60% men) who underwent MV repair or replacement for severe MR due to MV prolapse or chordal avulsion. Transthoracic echocardiography and Holter monitoring were performed in all patients before and annually after surgery. A pathomorphological study of MV fragments excised during surgery was performed. Results During the five-year follow-up period (144 person-years), one case of sudden cardiac death outside a health care facility was recorded. MR severity progressed in three patients after MV repair. The total number of all VAs decreased during the follow-up period, with a significant decrease in the number of paroxysms of unstable ventricular tachycardia during the first two years after surgery. The presence of VA in the postoperative period was correlated with the severity of postoperative left ventricular (LV) remodeling: end-diastolic volume (EDV) (rs=0.69; p=0.005), LV ejection fraction (EF) (rs = -0.55; p=0.004) and severity of MV myxomatous alterations according to histological study data (rτ=0.58; p=0.045). The beta-blocker treatment did not influence the VA frequency and severity (rs= -0.18; p=0.69). According to a univariate regression analysis only EDV (p = 0.001), LVEF <50% (p = 0.003), and myxomatous MV degeneration (p = 0.02) were risk factors for persistent ventricular tachycardia in the postoperative period. Conclusion Surgical intervention on MV in patients with MV prolapse and severe MR decreased the number of cases of malignant VAs and was correlated with the postoperative changes in LV volume and function, as well as the severity of MV myxomatous alterations.

The paper discusses the modern state of the mitral valve prolapse (MVP) problem. Controversial and unresolved issues on terminology, diagnostics, and tactics for different MVP variants are considered on the basis of the “Heritable disorders of connective tissue” recommendations (2009) by Expert Committee, the Society of Cardiology of the Russian Federation (VNOK). The modern diagnostic criteria of MVP are discussed, as well as echocardiography-estimated MVP prevalence while using those diagnostic criteria, and the comparison of Framingham Heart Study results to the authors’ own data. The interrelation between autonomic dysfunction and MVP is assessed, and different approaches to the stratification of MVP complication risk are compared, based on the echocardiography results and clinical data. The modern methods of MVP treatment and management strategy are also described.

Abstract Growing evidence supports role transforming growth factor-β (TGF-β) as a mediator of the myxomatous changes in the mitral valve prolapse. Recently, angiotensin II receptor blockers (ARB) emerged as a potentially effective inhibitor of TGF-β signaling. Treatment of valvular interstitial cells (VICs) with ARB resulted in effective inhibition of TGF-β-induced ECM expression. Our aim was to evaluate the effect of preoperative ARB therapy in modulation of transforming growth factor-β effects on mitral valve myxomatous degeneration. Methods A total of 233 asymptomatic patients (mean age: 53.8±12.9) undergoing mitral valve surgery for severe mitral regurgitation due to mitral valve prolapse were enrolled in our retrospective, non-randomized, single-center study. Resected abnormal segments of the mitral leaflets (segment of the posterior leaflet or the entire valve) were obtained during mitral valve repair/replacement surgery and examined by experienced pathologists. Immunohistochemical characterization of mitral valve sections was performed with the primary antibodies. Quantification was performed by counting TGF-β1 and TGF-β2 positive cells within 10 random high-power fields divided by the total number of cells in specimens. Quantification of immunohistochemical staining for collagen III was performed by measurement of staining area divided by the total area of the specimens. Results Two hundred thirty-three consecutive patients (66% males, mean age 53.8±12.9 years, range 19–80) with severe MR were enrolled in the study. According to the case reports, 43 patients (18.5%) received losartan or telmisartan before surgery and were included in study group. 190 patients (81.5%) did not receive any ARB and were enrolled in the control group. Histological examination showed disorganized collagen and elastin fibers, expansion of the spongiosa layer in both groups. However, MV specimens' immunohistochemistry revealed a lower expression of type III collagen in ARB group as compared to controls (31.3% ± 10.8% vs. 43.8% ± 15.3%; p<0.001). MV leaflets in control group showed the increased VICs density (95.3±39.9 vs. 70.0±21.7/high-power field, p=0.0001). TGF-β1 and TGF-β2 positive cells were significantly rare in the ARB than in control MV specimens (18% vs. 33%, p=0.012 and 16% vs. 38%, p<0.ehab724.15541, respectively). Expression of type III collagen and TGF-β2 positive cells count showed a weak, but significant correlation (r=0.28; p=0.ehab724.155414). The multivariate Cox analysis showed a decrease in the relative risk of valvular thickening (myxomatous degeneration) with ARB therapy (0.85; 95% CI: 0.61 – 1.17; p=0.01). Conclusions We indicate a beneficial effect of ARB treatment through the inhibition of TGF-β pathway on valvular myxomatous degeneration in patients with MVP. Modulation of the progression of MVP with such therapeutic agents may have great clinical significance. Funding Acknowledgement Type of funding sources: None.

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Improvement in malignant ventricular arrhythmias (VA) has been reported after mitral valve surgery in some mitral valve prolapse patients (MVP) with severe degenerative mitral regurgitation. Mitral annular disjunction, posterior systolic curling, and mitral annular abnormal contractility are associated with arrhythmic MVP and underwent correction during the mitral valve repair. However, mitral valve disease progression and ventricular arrhythmic substrates (left ventricular fibrosis of papillary muscles and basal posterior wall) could be potential substrates for persistent malignant arrhythmias even after surgical correction. Our aim was to evaluate the risk factors of persistent VA after mitral valve repair in Barlow’s disease patients in six-year follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) who underwent mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results All patients survived the operation. There was only one sudden cardiac death on sixth year of follow-up. During 173 person-years of follow-up 3 patients (10%) had developed recurrent moderate to severe (≥2) MR. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVCs and VT correlated strongly with postoperative end-diastolic LV diameter (EDD rs=.69; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.001). Advanced myxomatous degeneration assessed by pathologists and MV posterior leaflet’s thickness ≥5 mm after repair assessed by echocardiographer associated with postoperative PVCs and VT (rτ=.58; p=.045 and rs=.62; p=.002, respectively). Recurrent MR also strongly associated with postoperative PVCs and VT (rs=.76; p=.0018). In univariate analysis, advanced myxomatous degeneration (p=.008), postoperative end-diastolic LV diameter (p=.001), and low EF (p=.003) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Advanced myxomatous degeneration assessed by pathologists or echocardiographer and postoperative left ventricular remodeling are associated with persistent malignant ventricular arrhythmias. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmias is needed.

Abstract Introduction There is limited data on the efficacy of surgical repair in reducing ventricular arrhythmia (VA) in mitral valve prolapse (MVP) patients. Improvement in malignant ventricular arrhythmias has been reported only in isolated cases after mitral valve surgery. Our aim was to evaluate the possible effects of mitral valve repair on left ventricular (LV) reverse remodeling and incidence of VA in MVP patients in mid-term follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) undergoing mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography extended with speckle-tracking echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. Atrial fibrillation, PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results During 144 person-years of follow-up no deaths, and 3 cases (10%) of recurrent moderate or severe (≥2) MR occurred. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVC and VT correlates strongly with postoperative end-diastolic LV diameter (EDD rs=.70; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.01), but not postoperative MR (p>.05). EDD (58.8 ± 7.6 mm vs. 49.9 ± 5.6 mm; p=.00001) and EDV (156.6 ± 32.1 ml vs. 104.1 ± 22.8 ml; p=.00001) decreased in 1st year after repair with non-significant changes in EF (63.8 ± 12.8% vs. 59.6 ± 14.5%; p=.20), global systolic longitudinal strain –13.8 ± 2.5% vs. –14.6 ± 2.7%; p=.20) and SR (–0.93 ± 0.12 s-1 vs. –0.98 ± 0.13 s-1; p=.09) values. In univariate analysis, postoperative end-diastolic LV diameter (p=.001), low EF (p=.003), myxomatous degeneration (p=.008) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Mitral valve repair in MVP with severe mitral regurgitation is associated with reduction in ventricular arrhythmia, which strongly correlates with postoperative LV dimensions and function. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmia is needed.

Current understanding of the pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MS) focuses upon abnormal activity of the transforming growth factor beta (TGF-β) signalling pathway. Circulating TGF-β predicts cardiovascular events in patients with MS and is elevated in the entire spectrum of aortic syndromes. Marfanoid habitus (MH) patients not meeting the MS criteria (TAA, ectopia lentis, family history), but share the same skeletal features and are the part of the Marfan continuum. Our aim was to evaluate the possible role of elevated TGF-β level in the aortic dilatation at mid-term follow-up in Marfanoid habitus patients. 33 consecutive patients with a presumptive clinical diagnosis of Marfan syndrome were referred to Almazov centre and enrolled in our observational, prospective, single-center study. Nine of them (mean age 27.9 ± 9.3) fulfilled diagnosis of MS according to revised Ghent criteria. 24 subjects (mean age 21.8 ± 3.4) with skeletal features of Marfanoid habitus have had no major findings of MS. Proximal aortic segments were visualized in the parasternal long-axis and suprasternal views. Concentration of TGF-β1 and TGF-β2 in serum was determined using a test system Human Platinum ELISA. End points analyzed during 5 years of follow-up were mortality, aortic-related events, and aortic dimension changes. During 122 person-years of the follow-up (median 5.1 years) no deaths or aortic-related events occurred in Marfanoid habitus patients. TGF-β1 and TGF-β2 serum levels were elevated in patients with Marfanoid habitus (14.2 ± 27.6 and 2.1 ± 1.7 ng/ml, respectively) but were lower than in MS group (44.6 ± 47.3 ng/ml, p = 0.03 and 2.7 ± 1.7 ng/ml, p = 0.39, respectively). A high TGF-β1 serum level (cutoff >14.75 ng/ml, provided by the manufacturer of our TGF-β assay) was detected in 44% and TGF-β2 (>2.0 ng/ml) in majority patients (67%) of the MS group. In Marfanoid habitus group we found a high TGF-β1 serum level only in 4 (17%) patients and TGF-β2 in 9 (38%) patients. Aortic diameter at the sinuses of Valsalva and Z-score were significantly lower in Marfanoid habitus group (29.2 ± 2.8 mm and 1.56 ± 0.93) than in MS patients (43.1 ± 15.1 mm, p = 0.0007 and 6.86 ± 5.83, p = 0.004) at the beginning of study and significantly increased during the follow-up (31.3 ± 2.9 mm and 1,69 ± 0,15, p < 0.001 for both). There was no correlation between TGF-β level and aortic dimensions in patients with MS and marfanoid habitus. In young adults with Marfanoid habitus and the current absence of ascending aortic aneurysm we found the increased TGF-β level and aortic root enlargement during the follow-up. High TGF-β serum level may contribute to the excessive progression of aortic dilatation later over mid-to-late aging and requires further investigation to establish its role in the aortic aneurysm pathogenesis.

To assess the normal ranges of heart rate, PQ interval, QT interval, as well as to reveal cardiac arrhythmias typical for healthy subjects, the analysis of ECG Holter monitoring data of 200 healthy persons (69 women and 131 men) aged 30.78±0.77 years (16 52 years) was made.

Abstract Introduction Transforming growth factor-β1 (TGF-β1) is a crucial regulatory cytokine that contributes to the development of the mitral valve and regulates extracellular matrix protein synthesis in syndromic and non-syndromic mitral valve prolapse (MVP). Our aim was to evaluate the effect of elevated circulating TGF-β level on the progression of the valve myxomatosis and leaflets billowing at long-term follow-up. Methods 78 asymptomatic young subjects (mean age 19.7±1.6, 72% male) with MVP were consecutively enrolled in our observational, prospective, single-center study. MVP was diagnosed by billowing one or both mitral leaflets >2 mm above the mitral annulus in the long-axis parasternal view. Concentration of TGF-β1 in serum was determined by enzyme-linked immunosorbent assay using a test system Human Platinum ELISA. Results During 1170 person-years of follow-up (median 14.5 years), no deaths or MVP-related events occurred. Posterior leaflet's thickening (from 3.9±1.4 mm to 4.4±1.7 mm (D=+0.5 mm), p<0.01) and increase of the billowing (progression in maximal prolapse depth from 3.5±2.4 mm to 4.8±2.8 mm (D=+1.3 mm), p<0.001) leads to the mitral regurgitation (MR) progression (vena contracta: 2.3±0.4 mm vs. 3.5±0.4 mm (D=+1.2 mm), p<0.0001) over 15 years of follow-up. TGF-β1 serum level was increased (15.2±12.3 ng/ml) and strongly correlated with the thickening of the posterior leaflet (r=0.72; p≤0.0001). In multivariate Cox analysis the TGF-β1 level was the independent predictor of the posterior leaflet's thickening (2.07; 95% CI: 1.34 – 3.29; p=0.001) and progression of the billowing (2.89; 95% CI: 1.61 – 4.37; p=0.0001). TGF-β1 >7.0 ng/ml was a strong predictor (area under ROC curve = 0.84 (95% CI, 0.7–0.9); sensitivity 82%, specificity 95%) for progression of MVP (maximal prolapse depth increase: D +1.9±1.2 mm (TGF-β1 >7.0 ng/ml) vs. 0.7±0.6 mm (TGF-β1 <7.0 ng/ml), p<0.0001) and MR (vena contracta increase: D +1.1±0.5 mm (TGF-β1 >7.0 ng/ml) vs. 0.5±0.4 mm (TGF-β1 <7.0 ng/ml), p<0.0001). Conclusions Despite the overall benign prognosis, we found the obvious echocardiographic progression of the valve myxomatosis and leaflets billowing at long-term follow-up in young person. Elevated above 7.0 ng/ml TGF-β1 serum level might serve as a prognostic biomarker and identifies patients with increased risk of the mitral valve prolapse progression. Funding Acknowledgement Type of funding sources: None.

The review presents the current state and perspective of diagnosis of the most common forms of inherited disorders of connective tissue - mitral valve prolapse, and aortic aneurysm. The new classification of borderline dysplastic phenotypes has been presented. Diagnostic algorithm of marfanoid habitus and its main clinical manifestations were discussed.

Purpose: Ventricular arrhythmias are known to be common in symptomatic patients with Mitral Valve Prolapse (MVP). The aim of our study was to investigate the prevalence, echocardiographic and biochemical predictors, and possible mechanisms of ventricular arrhythmias in young asymptomatic patients with MVP without significant mitral regurgitation.

OBJECTIVE To evaluate left ventricular function in young adults with mitral valve prolapse (MVP) without significant mitral regurgitation using two-dimensional strain imaging. METHODS AND RESULTS A total of 58 asymptomatic young subjects (mean [± SD] age 19.7±1.6 years; 72% male) with MVP were compared with 60 sex- and age-matched healthy subjects. MVP was diagnosed by billowing one or both mitral leaflets >2 mm above the mitral annulus in the long-axis parasternal view. Longitudinal, radial and circumferential strain and strain rate were determined using speckle tracking with a grey-scale frame rate of 50 fps to 85 fps. There were no significant differences in the global systolic left ventricular function of the subjects with MVP compared with the control group. In the MVP group, most of the global myocardial systolic deformation indexes were not reduced. Only the global circumferential strain showed a decrease in the prolapse subjects. Regional, longitudinal, circumferential and radial strain and strain rate were decreased only in septal segments. A decrease in the rotation of the same septal segments at the basal level was also observed. CONCLUSION Regional septal myocardial deformation indexes decrease in subjects with MVP. These changes may be the first sign indicating the deterioration of left ventricular systolic function as well as the existence of primary cardiomyopathy in asymptomatic young subjects with MVP.

The paper attempts to revise the working classification of minor heart anomalies (MHA). It is proposed to exclude some syndromes and abnormalities which clearly have an independent clinical significance. The need for exclusion of prevalent normal variants, as well as anatomical and physiological characteristics of child’s heart, is justified. The inverse dynamics of selected MHA in older vs. younger age groups is demonstrated. The authors suggest that the current working classification should be modified.

To study prevalence of syndromes and phenotypes of dysplasia in healthy young adults and to study correlations between the number of bone signs as well as the heart rhythm parameters and the prevalence of arrhythmias, 111 subjects aged 20.2±1.7years (18 25 years) including 37 males and 74 females were examined.

The paper presents echocardiography examination results in healthy young people. The prevalence of classic and nonclassic mitral valve prolapse (MVP) is assessed. The prevalence of primary myxomatous MVP is independent of gender or age, while non-classic MVP is more prevalent in younger individuals. The mitral valve morphology is compared to that observed in the Framingham Study. The potential of color Doppler M-ultrasound is assessed for late systolic mitral regurgitation diagnostics in MVP.

The paper presents echocardiography examination results in healthy young people. The prevalence of classic and nonclassic mitral valve prolapse (MVP) is assessed. The prevalence of primary myxomatous MVP is independent of gender or age, while non-classic MVP is more prevalent in younger individuals. The mitral valve morphology is compared to that observed in the Framingham Study. The potential of color Doppler M-ultrasound is assessed for late systolic mitral regurgitation diagnostics in MVP.

The heritable connective tissue disorders with common general phenotypical and clinical features should be called dysplasia of the connective tissue. Classification of the basic dysplastical syndromes and phenotypes is offered. Article considers the algorithm of diagnostics of the basic syndromes and phenotypes and the practical questions arising at attempt of their classification.