Mitral Valve Defects Research Articles

Mutation in PDGFRbeta: a potential new pathogenic variant for acquired mitral valve prolapse

Abstract Funding Acknowledgements None. Background Mitral valve prolapse (MVP) due to myxomatous degeneration is characterized by familial clustering, but few pathogenic genes have been identified. In a genetic screening program for MVP patients, we identified a platelet-derived growth factor receptor β (PDGFRβ)-E162K missense variant in a family with a bi-leaflet MVP phenotype in four affected family members. PDGFRβ is a receptor tyrosine kinase, which plays an important role in vascular development. Purpose In this study, we investigated whether the E162K substitution in PDGFRβ could lead to mitral valve abnormalities. Methods To assess the functional effects of the missense variant, proliferation and migration assays were performed using HeLa cells overexpressing wild-type (WT) or mutant PDGFRβ. Immunostainings were performed to determine PDGFRβ expression in the diseased valves from a family member undergoing surgical operation and from additional patients operated for MVP. Mouse models were created with the mouse equivalent of the human PDGFRβ-E162K variant (PDGFRβ-E161K) using CRISPR/CAS9. The variant was not lethal and transthoracic echocardiography was performed on adult homozygous PDGFRβE161K/E161K mice, heterozygous PDGFRβE161K/- mice, and WT mice . In addition, histology was performed in adult and neonatal mice to detect potential valvular defects. Results HeLa cells expressing PDGFRβ-E162K and stimulated with PDGFD showed reduced proliferation and migration, suggesting a loss of function of the mutant receptor. PDGFRβ was expressed in human diseased mitral valves. Echocardiographic evaluation revealed a significant larger mitral valve annulus diameter in both PDGFRβE161K/- and PDGFRβE161K/E161K compared to WT (WT: 1.97 mm; PDGFRβE161K/-:2.13, p=0.031; PDGFRβE161K/E161K:2.42 mm, p<0.0001). Histological data in PDGFRβE161K/E161K mice showed significant leaflet thickening in the free edge (FE) of the posterior mitral valve leaflet (PMVL) compared to WT (WT: 72.34 ɥm; PDGFRβE161K/E161K: 109.6 ɥm, p=0.040) and a larger leaflet area of the PMVL compared to WT (WT: 25280 ɥm²; PDGFRβE161K/E161K: 44494 ɥm², p=0.020). Moreover, an altered organization of the extracellular matrix reminiscent of the myxomatous degeneration in MVP was observed. These alterations were not observed in mutant neonatal hearts. Conclusions The PDGFRβ-E162K variant is associated with familial MVP and alters the function of PDGFRβ. Mice harboring this mutation display acquired mitral valve defects.

Gustav Mahler: tragic life, mysterious illness, early death : Could intensive care medicine have saved him today?

Gustav Mahler was a composer of the late Romantic period, one of the most famous conductors of his time and, as opera director, one of the most important reformers of musical theatre. Mahler's life, illnesses, death and dying are little or not at all known to many. Which illnesses determined Mahler's life? Could his early death have been avoided? From today's point of view, could modern intensive care medicine have helped him? A detailed analysis of Mahler's diseases was performed using scientific databases (medline, pubmed). All published articles were examined in detail. Gustav Mahler was born in 1860 in Kalischt (Bohemia) and learned to play the accordion and piano at an early age. He studied music at the Vienna Conservatory from 1875 and completed his composition studies in 1878. Kapellmeister positions followed in several cities, from 1887 at the Vienna Court Opera and from 1908 at the Metropolitan Opera in New York. Mahler suffered from many illnesses, especially tonsillitis and haemorrhoids. In 1907 he was diagnosed with a mitral valve defect, in 1911 he developed bacterial endocarditis caused by streptococci, as a result of which Mahler died in Vienna in 1911. His life was marked by personal and health tragedies. Mahler was an outstanding personality who left behind an extensive oeuvre. Among the compositional highlights are his 10 symphonies and the song compositions. Recurrent streptococcal infections led to mitral valve disease and endocarditis, the consequences of which caused Mahler's untimely death. Today's modern cardiology and intensive care medicine could have prolonged his life, but unfortunately this was not possible at the time when he was diagnosed with endocarditis.

Predicting the Development of Complications After Mitral Valve Repair Using Mathematical Analysis

AIM. To study the possibilities of using risk factors, data from instrumental research methods identified at the preoperative stage as independent variables for predicting the development of complications after mitral valve surgery. MATERIAL AND METHODS. The study included 103 patients, 46 men and 57 women, who underwent surgical correction of mitral valve defect and were treated at the Cardiac Surgery Department of Chelyabinsk Regional Clinical Hospital № 1 in the period from 2014 to 2019. Among those patients, the presence of anemia at the preoperative stage (blood hemoglobin level less than 100 g/l) was detected in 13 (12,6 %) cases; obesity (BMI more than 30 kg/m2) — in 57 (55,3 %) cases; transfusion of blood and its components in anamnesis — in 14 (13,6 %) cases; type 2 diabetes mellitus — in 7 (6,8 %) cases; stroke in anamnesis — in 9 (8,7 %) cases; chronic Hepatitis C — in 6 (5,8 %) cases; HIV infection — in 4 (3,9 %) cases; antibiotic therapy before surgery was indicated in 21 (20,4 %) cases; edema of the lower extremities was detected in 40 (38,8 %) cases; an increase in body temperature before surgery — in 19 (18,4 %) cases; the presence of atrial fibrillation before surgery — in 63 (61,2 %) cases. The systematization of the source information was entered into a Microsoft Office Excel 2016 spreadsheet. Statistical analysis was carried out using the IBM SPSS Statistics v.26 program (developed by IBM Corporation). Binary logistic regression was used as a method of mathematical data analysis. Instrumental research methods: electrocardiography (ECG), echocardiography (ECHO-CG); coronary angiography was performed according to indications. RESULTS. The presence of risk factors such as anemia, obesity, as well as an increase in the size of the right atrium can be used as an independent variable to predict the development of complications. An increase in the diameter of the pulmonary artery trunk, and the presence of edema of the lower extremities reduces the risk of complications. The likelihood of developing complications after mitral valve surgery predicted by the logistic regression method was 53,4 %. The resulting model predicts the absence of complications with the likelihood of 82,5 %. The development of complications was correctly predicted in 93,3 % of cases. CONCLUSION. This model can be used as an additional tool in predicting the development of complications after mitral valve surgery.

Understanding the cell fate and behavior of progenitors at the origin of the mouse cardiac mitral valve

Congenital heart malformations include mitral valve defects, which remain largely unexplained. During embryogenesis, a restricted population of endocardial cells within the atrioventricular canal undergoes an endothelial-to-mesenchymal transition to give rise to mitral valvular cells. However, the identity and fate decisions of these progenitors as well as the behavior and distribution of their derivatives in valve leaflets remain unknown. We used single-cell RNA sequencing (scRNA-seq) of genetically labeled endocardial cells and microdissected mouse embryonic and postnatal mitral valves to characterize the developmental road. We defined the metabolic processes underlying the specification of the progenitors and their contributions to subtypes of valvular cells. Using retrospective multicolor clonal analysis, we describe specific modes of growth and behavior of endocardial cell-derived clones, which build up, in a proper manner, functional valve leaflets. Our data identify how both genetic and metabolic mechanisms specifically drive the fate of a subset of endocardial cells toward their distinct clonal contribution to the formation of the valve.

Rare case of unileaflet mitral valve diagnosed by computed tomography

Introduction. Congenital malformations of the mitral valve encompass a broad spectrum of lesions, with an incidence of approximately 0.4% among patients with congenital heart diseases. Case Report. A 45-year-old female was admitted to our institution due to a confirmed mitral valve defect identified via echocardiographic examination. She presented with leg swelling and rapid fatigue. Her medical history includes systemic lupus erythematosus. Upon admission, she was in cardiopulmonary decompensation, with a systolic murmur detected in the mitral valve area, radiating towards the axilla. Transesophageal echocardiographic revealed severe mitral stenosis with moderate regurgitation, without clear visualization of the two cusps. Cardiac computed tomography confirmed a voluminous anterior mitral cusp and a hypoplastic posterior cusp, observed in diastole as a crescent-shaped, characteristic of a unicuspid mitral valve. Follow-up echocardiographic showed progression of mitral regurgitation with circumferential pericardial effusion, necessitating pericardiocentesis. Due to further hemodynamic instability, urgent surgical mitral valve replacement was indicated. The surgery proceeded without complications, but the immediate period was marked by exacerbation of renal impairment, requiring hemodiafiltration on several occasions. Following cardiological stabilization, the patient was transferred to the Nephrology Clinic for further management of renal insufficiency and systemic lupus. Conclusion. It is crucial to emphasize the significance of a multidisciplinary approach for each patient, with particular emphasis on detailed imaging diagnostics to definitively establish a congenital heart disease diagnosis.

Midterm outcomes of the Ozaki procedure in patients with a bicuspid aortic valve: retrospective single-center, non-randomized, parallel-group study

BACKGROUND: An alternative to plastic surgery on the bicuspid aortic valve (BAV) can be replacement of the leaflets with autopericardium using the Ozaki technique. The procedure is characterized by excellent hemodynamic results in the short and long term in patients with tricuspid aortic valve (TAV). However, the question remains about the long-term results of the procedure and the frequency of reoperations in patients with BAV.
 OBJECTIVE: To analyze the midterm outcomes of the Ozaki procedure in patients with BAV.
 MATERIALS AND METHODS: Retrospective single-center, non-randomized, parallel-group study was conducted. Since January 2015 to October 1, 2023, the clinic performed 809 Ozaki procedures. The work included 540 patients with studied midterm and long-term outcomes for up to 5 years. Both isolated aortic valve replacement and combined operations with coronary artery bypass grafting and (or) correction of mitral and tricuspid valve defects were performed.
 RESULTS: Midterm mortality was 5.7% (n=3) in the group with BAV and 7.3% (n=36) in the group with TAV. Reoperation for aortic regurgitation was required in 16 patients (2.9%): 1 patient (1.9%) in BAV group and 15 (3.3%) in TAV group. Freedom from reoperations in patients with BAV after the Ozaki procedure for up to 5 years was 95.4%, in the group with TAV — 92.6%. The peak gradient on the aortic valve in the group with BAV was 16±7.3, in TAV group— 16.4±10.9. 5 years after surgery, the mean gradient on the aortic valve does not exceed 10 mm Hg.
 CONCLUSION: The Ozaki operation in patients with BAV is an effective and safe procedure in the midterm follow-up period.

The role of TBX20 truncating variants in dilated and left ventricular non-compaction cardiomyopathy

Abstract Background The genetic cause of dilated cardiomyopathy (DCM) remains unexplained in a considerable proportion of cases. TBX20, the T-Box transcription factor 20 gene, has been linked to cardiac septal defects. Although only a few case reports have described an association between TBX20 and DCM/left ventricular non-compaction (LVNC), there are no case-control studies available, and TBX20 is still considered a gene with limited evidence for these phenotypes. Objectives This study sought to investigate the relationship between truncating variants in TBX20 (TBX20tv) and the development of DCM and LVNC. Methods TBX20 was sequenced using massive parallel sequencing in 7,463 unrelated probands with DCM/LVNC and 22,773 probands with other diagnoses (e.g., hypertrophic or arrhythmogenic cardiomyopathy, channelopathies, or aortic diseases) as internal controls. It was tested for enrichment and cosegregation of TBX20tv in DCM/LVNC, and clinical characteristics and outcomes in carriers were analyzed. Results Twenty-four probands with 22 TBX20tv were identified. Variant frequencies were significantly higher in patients with DCM/LVNC (24/7,463; 0.29%) than in internal controls (2/22,773; 0.008%) or controls from the gnomAD database (4/124,098; 0.003%), with an OR of 70.18 (CI95%: 9.48 to 519.8; p <0.0001) and 95.61 (CI95%: 33.06-276.55; p <0.0001), respectively. Cosegregation was studied in 21 families, identifying 57 carriers, of whom 43 (75.4%) had cardiac involvement. A combined LODs score of 4.41 was obtained, which is indicative of very strong segregation. Regarding clinical characteristics, the mean age at diagnosis was 37 years old, and 50% of carriers were female. Forty-six percent developed left-ventricular dysfunction, which was moderate to severe in half of the cases. Three carriers received a heart transplant, and another carrier died due to heart failure. Congenital heart defects were present in 16 patients (28.1%). Valvular involvement was the most frequent congenital abnormality (5 cases had bicuspid aortic valve, and another 5 had mitral valve defects), followed by heart septal defects (3 atrial and 3 ventricular); coronary anomalies (2) and aortic coarctation (2) were also detected. In some patients, these defects presented as complex congenital heart disease. Conclusions TBX20tv are associated with the development of dilated and non-compaction cardiomyopathy, and the presence of congenital heart defects is also common. Although some carriers, particularly younger ones, may not present the phenotype, nearly half of them experience ventricular dysfunction, and significant cardiac events, such as cardiac death or transplantation, are not uncommon. Therefore, the TBX20 gene should be routinely included in genetic testing panels for DCM and LVNC.

Mutation in PDGFRbeta: a potential new pathogenic variant for mitral valve prolapse

Abstract Background Mitral valve prolapse (MVP) due to myxomatous degeneration is characterized by familial clustering, but few pathogenic genes have been identified. In a genetic screening program for MVP patients, we identified a platelet-derived growth factor receptor β (PDGFRβ)-E162K missense variant in a family with a bi-leaflet MVP phenotype in four affected family members. PDGFRβ is a receptor tyrosine kinase, which plays an important role in vascular development. Purpose In this study, we investigated whether the E162K substitution in PDGFRβ could lead to mitral valve abnormalities. Methods To assess the functional effects of the missense variant, proliferation and migration assays were performed using HeLa cells overexpressing wild-type (WT) or mutant PDGFRβ. Immunostainings were performed to determine PDGFRβ expression in the diseased valves from a family member undergoing surgical operation and from additional patients operated for MVP. Mouse models were created with the mouse equivalent of the human PDGFRβ-E162K variant (PDGFRβ-E161K) using CRISPR/CAS9. The variant was not lethal and a total of 12 homozygous PDGFRβ-E161K-/- mice, 11 heterozygous PDGFRβ-E161K+/- mice, and 7 WT mice were subjected to transthoracic echocardiography. In addition, histology was performed in all 30 mice to detect potential valvular defects. Results Stimulated HeLa cells expressing PDGFRβ-E162K showed reduced proliferation and migration, suggesting a loss of function of the mutant receptor. PDGFRβ was expressed in human diseased mitral valves. Echocardiographic evaluation revealed a significant larger mitral valve annulus diameter in both PDGFRβ-E161K+/- and PDGFRβ-E161K-/- compared to WT (WT: 1.97 mm; PDGFRβ-E161K+/-:2.13, p=0.031; PDGFRβ-E161K-/-: 2.42 mm, p<0.0001). Histological data in PDGFRβ-E161K-/- mice showed significant leaflet thickening in the free edge (FE) of the posterior mitral valve leaflet (PMVL) compared to WT (WT: 72.34 ɥm; PDGFRβ-E161K-/-: 109.6 ɥm, p=0.040) and a larger leaflet area of the PMVL compared to WT (WT: 25280 ɥm²; PDGFRβ-E161K-/-: 44494 ɥm², p=0.020). Moreover, an altered organization of the extracellular matrix reminiscent of the myxomatous degeneration in MVP was observed. Conclusions The PDGFRβ-E162K variant is associated with familial MVP and alters the function of PDGFRβ. Mice harboring this mutation display mitral valve defects and can be used as a model for mitral valve disease.

Dynamics of anxiety, depression, and quality of life after early physical rehabilitation of patients who underwent surgical correction of acquired mitral valve defect: clinical prospective randomized study

BACKGROUND: The activation of the patient from the day after an acquired mitral valve (MV) defect with standard cardiorehabilitation surgery and further physical training at an early uncomplicated inpatient stage of the postoperative period appears promising to improve not only the functional status but also the quality of life (QL).
 AIM: Our aim was to examine the effect of early physical rehabilitation on the dynamics of anxiety, depression, and QL in patients after surgical correction of the MV defect.
 MATERIALS AND METHODS: The study included 80 patients (median age 60.8 [47.5; 69.0] years) who underwent surgical correction of an acquired MV defect. Starting from the 7th day after the surgery, patients were assessed for functional status, and the intensity of the training load was selected, and this was done again on the 24th day after the surgery. Moreover, the QL parameters on the SF-36 scale and levels of anxiety and depression on the Hospital Anxiety and Depression Scale (HADS) were evaluated. The control group (n=47) underwent a standard cardiac rehabilitation program from 1st day after surgery. In the main group (n=33), based on the results of the cardiopulmonary exercise testing, physical training on a treadmill was initiated for 14 days, from the 8th day after the surgery, in addition to a personalized training program.
 RESULTS: In addition to improving the functional state, early physical training improved the dynamics of QL indicators in the main group. After 14 days of treadmill training, the physical health component increased from a median of 35.1 to 64.4 (p=0.03), and the mental health component from a median of 49.1 to 82.1 (p=0.03). In addition, after the early physical rehabilitation program in the main group, the number of people without anxiety and depression, according to the HADS scale, significantly increased from 9% to 27.3% (p=0.04), whereas the dynamics of the QL, anxiety, and depression levels in the control group were not significant.
 CONCLUSION: Early physical rehabilitation, including moderate-intensity workouts with an individual calculation of the speed / angle of the treadmill, starting from 8 days after surgical correction of the acquired MV defect demonstrated efficacy in improving the QL and reducing anxiety and depression levels 24 days after surgery.

Specificity of long-term management of a woman patient of reproductive age after surgical mitral valve repair against the background of infective endocarditis

As a clinical case, we present the "portrait" of a woman patient with acquired mitral valve (MV) defect against the background of infective endocarditis which was diagnosed during the third trimester of pregnancy. The patient underwent mitral valve replacement surgery with biological prosthesis "KemKor" followed by two successful deliveries. In 18 years after the correction of the mitral valve defect, she developed valve prosthesis dysfunction therefore, she underwent endovascular transcatheter implantation of bioprosthesis by method "prosthesis-into-prosthesis" in the mitral position.This clinical case is unique in terms of the reasoning the biological prosthesis choice to correct acquired MV defect in a patient of reproductive age, the long-term period of the bioprosthesis functioning and the correction of further developed valve dysfunction using the techniques of transcatheter implantation.

Congenital mitral valve defects in pediatric population: a narrative review of surgical repair

Background and Objective: Congenital mitral valve malformations (CMVM) are rare and heterogeneous. The functional classification includes mitral regurgitation, stenosis, and combined lesions. Surgical strategies of CMVM remain challenging in the pediatric population due to various malformations, growth potential, the requirement of long-term anticoagulation, and the necessity of avoiding or delaying valve replacement. Surgical techniques for CMVM must be individually tailored for patients to achieve a proper valve function rather than “normal” anatomy. Compared with mitral repair, mitral valve replacement (MVR) is a less common procedure in children due to high mortality and morbidity rates. Options for cardiac valve replacement in children are limited to prostheses sizes that do not accommodate somatic growth, especially for neonates and infants. The need for lifelong anticoagulation may lead to adverse long-term pregnancy outcomes for female patients, limiting the application of MVR. This review aims to provide a comprehensive analysis of the current surgical techniques and developments for treating mitral valve (MV) regurgitation and stenosis and the outcome of various surgical strategies.

A case report of successful surgical treatment of mitral valve disease 38 years after implantation of ball-valve mechanical prosthesis in aortic position

The application of ball-valve prostheses in clinical practice marked a new age in the treatment of valvular heart pathology. Ball-valve prostheses are made of long-living and hard-wearing materials; however, these properties confer significant disadvantages resulting from the large dimensions and weight, increased pressure gradient and risk of valve thrombosis and systemic embolism. With the advent of more advanced disk structures, the use of ball-valve prostheses was ended.In Russia and other counties, the scientific literature shows an increase in reoperation after implantation of ball-valve prostheses over the long-term, which is associated with the occurrence of another valve defect. The need to replace a functioning ball-valve prosthesis with a modern mechanical or biological prostheses during surgery for another valve is still controversial.We present a case report of a 55-year-old patient with rheumatic mitral stenosis and functional insufficiency of the tricuspid valve, who underwent repeat surgery 38 years after implantation of a ball-valve prosthesis in the aortic position. From the echocardiography findings, the peak transmitral gradient was 16 mm Hg, the average gradient was 5.5 mm Hg, the area was 1.3 cm2 and regurgitation was third-degree. On the tricuspid valve, there was third-degree regurgitation.Adequate hemodynamic parameters of the ball-valve prosthesis (the maximum blood flow rate was 2.65 m/sec, the peak gradient was 30 mm Hg, the average gradient was 18 mm Hg and there was no regurgitation) and the absence of valve-dependent complications enabled us to perform mitral prosthetics and tricuspid valve plastic surgery without replacing the aortic prosthesis, which reduced the operation time and decreased the risk of complications.The patient was examined two years later. The patient’s active lifestyle and adequate hemodynamic parameters proved the rationality of our treatment policy.The reported case indicates that mitral valve defect that develops a long time after aortic valve prosthetics can be treated surgically without the replacement of a ball-valve prosthesis in the case that it has good function.Received 25 July 2021. Revised 22 August 2021. Accepted 23 August 2021.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Contribution of the authors: The authors contributed equally to this article.

Absence of Pericardium in Combination with Myocardial Noncompactness (Literature Review; Clinical Case Description)

Introduction. Cardiovascular diseases (CVD) in all epidemiological indicators continue to hold a leading position not only in Ukraine but also around the world and are a global medical and social problem. In the first place, such positions are provided by coronary heart disease (CHD) - the most common variant of SSC, despite the significant advances in modern clinical medicine. At the same time, sometimes the verification of the diagnosis is delayed or it is not possible to establish it during life, which contributes to the hyper- or hypodiagnosis of the most common nosologies, forgetting about diseases that are extremely rare. The aim of the study. To make the review of the literature and the description of a clinical case for the purpose of clarification of features of a clinical condition and diagnostics at patients with congenital absence of a pericardium in combination with noncompactness of a myocardium. Materials and methods. Content analysis, method of system and comparative analysis, bibliosemantic method of studying current scientific researches concerning studying of congenital absence of pericardium in combination with noncompactness of myocardium are used. Sources were searched in scientometric databases: PubMed, Medline, Springer, Google Scholar, Research Gate by keywords: congenital absence of pericardium, not myocardial compactness. 51 sources in English and Ukrainian were selected and analyzed, which covered the epidemiology of congenital absence of the pericardium and myocardial compactness, their clinical and diagnostic features; described a clinical case. Results. Congenital absence of the pericardium is a rare congenital anomaly of the pericardium, which, depending on the extent of the defect is left-handed (from 0.0001 % to 0.044 % in the population and in 70.0 % of all cases of congenital absence of the pericardium), right-handed and total (9.0 % of all cases) is more common in men than in women, respectively, as 3.0:1.3. During embryonic development, both the cardiac and pulmonary rudiments, the beginning of the formation of which begins in 3-4 weeks, are displaced from the cervical region into the thoracic cavity, going to the pericardial and pleural cavities, respectively. Premature atrophy of the left cuvier duct leads to non-separation of the pericardial cavity from the left pleural cavity. Due to these reasons, the absence of the left half of the pericardium is the most common. If pleuropericardial folds are not formed, the rudiments of the heart and lungs are in a single pleuropericardial cavity. Quite often, congenital absence of pericardium is associated with other congenital heart defects, for example, with a defect of the atrial septum (MPP), open ductus arteriosus, tetrad E.-L. Fallot, mitral valve stenosis, with defects of the diaphragm, lungs, kidneys. Most cases of this defect are asymptomatic and may not be diagnosed for life, so they can often be confused with other diseases such as heart aneurysm, coronary heart disease, mitral valve or atrial septal defects. Some informative signs may appear during X-ray diagnosis (radiograph may show convexity of the left upper border of the heart, high position of the heart), but the main emphasis in the diagnosis is on echocardiography (Echo-CG) (enlarged pancreas and right atrium), significant regurgitation tricuspid valve), magnetic resonance imaging (MRI), and the gold standard is the so-called multimodal imaging using multislice computed tomography (MSCT) (no visualization of the pericardial layer, rotation of the heart to the left, interposition of the pulmonary artery and lung tissue). At the same time, any of these techniques may have more or less pronounced shortcomings, which sometimes make it difficult to diagnose pericardial abnormalities. Myocardial noncompactness is a genetic malformation whose prevalence is not high, although its final prevalence cannot be established, as it is not uncommon for such individuals to have an asymptomatic course. On the ECG, myocardial noncompactness may be accompanied by supraventricular and ventricular arrhythmias, blockades of varying degrees, and one of the most accurate methods of visualizing myocardial noncompactness is Echo-CG. During this examination, two layers of the myocardium are visualized: subepicardial with a compact myocardium and subendocardial with a non-compact myocardium, and an important diagnostic and prognostic feature is the ratio of these layers at the end of systole. Conclusions. A review of the literature and described a clinical case of pericardial absence in combination with myocardial infarction. Elucidation of clinical features of absence of a pericardium in combination with incompatibility revealed that this anomaly is usually asymptomatic, however at patients with a left defect can be disguised under an ischemic heart disease, followed by ventricular arrhythmias (ventricular tachycardia), lengthening of a Q interval. Of particular value for the diagnosis of congenital absence of the pericardium in combination with myocardial infarction is Echo-CG and MRI, and the gold standard is considered to be MSCT, but these methods can sometimes have limited diagnostic capabilities. Keywords: congenital absence of pericardium, anomaly of the cardiac sac, myocardial non-compactness, prolonged QT interval.

"Portrait" of patients with pulmonary hypertension, associated with mitral valve diseases before cardiac surgery

Aim. To study “the portrait” of patients with acquired mitral valve (MV) heart disease of various origins and pulmonary hypertension hospitalized for surgical correction of the defect.Methods. The study included 97 patients with acquired diseases of mitral valve and pulmonary hypertension. The assessment of demographic, clinical and anamnestic data, indicators of transthoracic echocardiography, quality of life before the correction of MV defect was carried out.Results. The studied cohort is mostly represented by female patients (n = 70; 72.2%). The most common cause of mitral valve disease was rheumatic heart disease (n = 40; 41.2%). Overweight, hypertension (n = 76; 78.4%) and atrial fibrillation (n = 62; 63.9%) were the most common comorbidities. The mean pressure level in the pulmonary artery according to echocardiography was 35.5 (29.0; 40.0) mm Hg, with no significant difference among the patients, regardless the mitral defect etiology. Less pronounced remodeling of the left ventricle was noted in patients with rheumatic heart disease, which is caused by a lesion of the MV by the type of stenosis in contrast to patients with connective tissue dysplasia syndrome or against the background of detachment of MV chords with MV damage in the form of its insufficiency. There were no significant differences in the systolic function of the right ventricle depending on the etiology of MV defect.Conclusion. The “portrait” of a patient with pulmonary hypertension associated with an acquired mitral valve defect before its correction is the predominance of female, overweight, with II or III functional class of chronic heart failure, more frequent rheumatic genesis of MV defect, the presence of concomitant pathology in the form of hypertension and persistent atrial fibrillation, and increased size of the left atrium and left ventricle, reduced systolic function of the right ventricle according to the data of Echocardiography.

TAB2 deletions and variants cause a highly recognisable syndrome with mitral valve disease, cardiomyopathy, short stature and hypermobility.

Deletions that include the gene TAB2 and TAB2 loss-of-function variants have previously been associated with congenital heart defects and cardiomyopathy. However, other features, including short stature, facial dysmorphisms, connective tissue abnormalities and a variable degree of developmental delay, have only been mentioned occasionally in literature and thus far not linked to TAB2. In a large-scale, social media-based chromosome 6 study, we observed a shared phenotype in patients with a 6q25.1 deletion that includes TAB2. To confirm if this phenotype is caused by haploinsufficiency of TAB2 and to delineate a TAB2-related phenotype, we subsequently sequenced TAB2 in patients with matching phenotypes and recruited patients with pathogenic TAB2 variants detected by exome sequencing. This identified 11 patients with a deletion containing TAB2 (size 1.68-14.31 Mb) and 14 patients from six families with novel truncating TAB2 variants. Twenty (80%) patients had cardiac disease, often mitral valve defects and/or cardiomyopathy, 18 (72%) had short stature and 18 (72%) had hypermobility. Twenty patients (80%) had facial features suggestive for Noonan syndrome. No substantial phenotypic differences were noted between patients with deletions and those with intragenic variants. We then compared our patients to 45 patients from the literature. All literature patients had cardiac diseases, but syndromic features were reported infrequently. Our study shows that the phenotype in 6q25.1 deletions is caused by haploinsufficiency of TAB2 and that TAB2 is associated not just with cardiac disease, but also with a distinct phenotype, with features overlapping with Noonan syndrome. We propose the name "TAB2-related syndrome".

КОРРЕКЦИЯ ЖЕЛЕЗА ПРИ БЕСКРОВНЫХ ОПЕРАЦИЯХ У БОЛЬНЫХ С МИТРАЛЬНЫМИ ПОРОКАМИ СЕРДЦА

Objective. To study the effectiveness of the preoperative combined correction, using hydroxide of iron (III) and stimulation of hematopoiesis with erythropoietin on the postoperative anemia in patients, undergoning bloodless surgery (mitral valvere placement) in conditions of artificialblood circulation. Methods. A single-center prospective non-randomized and retrospective study involving patients (n=80) undergoning the operation for mitral valve disease was carried out. There were 54 men (67.5%) and 26 women (32.5%) with an average age of 52.8±4.9 years (M±σ). The patients were divided into three groups. Group A consisted of patients with normal serum iron levels undergoning of the application of blood component preparations. Group B included patients with normal serum iron levels who were undergoning bloodless surgery. In group C the patients with initially low levels of iron in the blood serum, preoperative correction of the saturating dose iron hydroxide and stimulation with erythropoietin were carried out, and bloodless procedure was applied while the operation. Results. The results of this study show that patients in group A require a sufficiently large volume of donor blood components during surgery. In group B, mitral valve replacement can be performed using bloodless technology without transfusion of donor blood components. Correction of a low preoperative serum iron level in group C increases its preoperative serum iron level by 7.4 times and Hb by 4.4% of the initial haemoglobin values. The level of postoperative anemia in group C (p>0.05) compared with group B (p>0.05) is 8.5% less (p>0.05). Conclusion. Correction of low preoperative iron levels and stimulation of erythropoiesis in patients with mitral heart disease after mitral valve replacement using a bloodless surgery reduces the postoperative anemia level. What this paper adds For the first time the impact of preoperative correction of anemia, using iron (III) hydroxide and stimulation of hematopoiesis, applying erythropoietin in patients undergoning the surgery for mitral valve defect using bloodless technology in conditions of artificial blood circulation (ABC) has been determined.

Original method of posterior aortoplasty for aortic valve replacement in surgical treatment of combined mitral-aortic valve diseases

Objective. To research of possibilities of reconstruction of aorta`s ostium and ascending aorta during aortic valve replacement and simultaneous correction of mitral valve defects at patients with narrow aorta`s ostium.
 Materials and methods. The study group consisted of 46 patients with mitral-aortic heart diseases and combination with a narrow aortic mouth, who were operated on at the A
 Amosov National Institute of Cardiovascular surgery for the period from January 1, 2006 to January 1, 2020. All patients underwent reconstruction of the aortic root and ascending aorta according to the original method of posterior aortoplasty. There were 26 men (56.5%) and 20 women (43.5%). The age of patients ranged from 23 to 72 years (average - 58.4±7.3 years). 8 (17.4%) patients belonged to class III NYHA, 38 (82.6%) - to class IV.
 Results. Of the 46 operated patients at the hospital stage (30 days after surgery), 4 died (hospital mortality 8.7%). No fatalities were associated with surgical technique. The dynamics of echocardiographic parameters at the hospital stage was as follows: the systolic gradient on the aortic valve was before surgery 112.1 ± 15.2 mm Hg, on the aortic prosthesis at discharge - 23.2 ± 6.4 mm Hg; end-systolic index (ESI) of the left ventricle (ml/m²) - 59.1 ± 7.6 (before surgery) and 48.3 ± 5.9 (after surgery); left ventricle ejection fraction (EF) - 0.45 ± 0.04 (before surgery) and 0.53 ± 0.04 (after surgery).
 Conclusions. The proposed original technique of posterior aortoplasty allows to effectively expand the mouth of the aorta for further implantation of an artificial heart valve of larger diameter. The technique is quite safe. At the hospital stage there are no complications directly related to the technique of operations. At the early postoperative period, the morphometric parameters of the left ventricle (EF and ESI) improved. The technique can be successfully used for the correction of combined mitral-aortic valve defects.

Коррекция дефицита антитромбина в периоперационном периоде у кардиохирургических пациентов

Введение: В качестве антикоагулянта у пациентов с сочетанием порока митрального клапана (МК) и ишемической болезнью сердца (ИБС) в периоперационном периоде используется гепарин. Терапевтическая активность гепарина зависит от уровня активности антитромбина (АТ). Дефицит АТ увеличивает риск тромбоза. Цель исследования: оценить эффективность и безопасность препаратной коррекции дефицита АТ в интраоперационном периоде у пациентов с сочетанием по рока МК и ИБС. Материалы и методы: Обследовано 30 доноров и 46 пациентов с ИБС и патологией МК. Измерение аналитов проводили на 3 этапах: до кожного разреза, после ушивания операционной раны, через 24 ч после начала операции. В зависимости от уровня активности АТ (cut-off 60%) пациенты с этапа 2 были разделены на 2 группы. Пациенты обеих групп получали лечение в соответствии со стандартным анестезиологическим протоколом, пациентам группы 2 дополнительно для коррекции дефицита АТ вводили препарат Антитромбин- III (Бакстер АГ, Австрия). Результаты: Не обнаружено разницы между группами по объему послеоперационной кровопотери, продолжительности искусственной вентиляции легких и времени пребывания в отделении реанимации и интенсивной терапии. Более низкая активность АТ в группе 2 сохранялась на всех этапах исследования. При нормировании снижения уровня АТ в группе 2 обнаружена более выраженная динамика. Аналогичные результаты получены для этапов 2 и 3 при нормировании восстановления активности АТ. Обнаружена умеренная отрицательная корреляция снижения активности АТ и времени пережатия аорты, уровня Д-димера и активности АТ на этапе окончания операции. Заключение: Исходная активность АТ у всех обследованных пациентов была ниже, чем в группе доноров. У пациентов с исходно низким уровнем АТ документирована более выраженная динамика его снижения. Восстановление активности АТ после препаратной коррекции его дефицита происходило значимо эффективнее. Пациентам с сочетанием порока МК и ИБС рекомендуется интраоперационная коррекция Антитромбином при снижении активности < 60% к моменту окончания операции. Применение препарата безопасно и не ведет к увеличению кровопотери. Background: Heparin is used as an anticoagulant perioperatively in patients with combined cardiac pathology. The heparin therapeutic activity depends on the level of antithrombin (AT) activity. AT defi ciency increases the risk of thrombosis. Objectives: to access the effectiveness and safety of drug correction of AT defi ciency in the intraoperative period in patients with combined mitral valve defect (MVD) and ischemic heart disease (IHD). Patients/Methods: 30 healthy blood donors and 46 patients with IHD and MVD were examined. The analytes were measured at 3 stages: before the skin incision, after suturing the operating wound, and 24 hours after the start of the operation. Depending on the AT activity at the second stage (cut-off 60%) patients were divided into 2 groups. All patients received treatment according to the standard anesthetic protocol; group 2 patients were given Antithrombin III (Baxter AG, Austria) to correct AT defi ciency. Results: There was no difference between the groups in the postoperative blood loss, duration of ventilation and ICU stay. The lower activity of AT in group 2 patients remained at all study stages. When the decrease in AT level was rationed, more pronounced dynamics was found in group 2. Similar results were found at stages 2 and 3 after the AT activity restoration also was rationed. Moderate negative correlation at the stage 2 was found between the drop of AT activity and the time of aortic clamping, and between the D-dimer level and AT activity. Conclusions: The initial AT activity in all examined patients was lower than in the blood donor group. In patients with an initially low AT level a more pronounced dynamic of its decrease was documented. Recovery of AT activity was significantly more effective after drug correction of its defi ciency. For patients with MVD and IHD combination intraoperative correction with Antithrombin is recommended if the activity decreases by < 60% by the end of the operation. The use of the drug is safe and does not lead to increased blood loss.

New Technique in Assessment of Heart Chambers Remodeling in Acquired Mitral Valve Defects.

Objective: Analysis and presentation of the capabilities of the new ultrasound technique —the index of volume remodeling (IRV), which allows comprehensive assessing of pathological remodeling of the heart as an integrated functional anatomical system. Materials and methods: For this study 316 patients with acquired mitral valve disease (MVD) were examined prior to and following mitral valve replacement with bileaflet, disc-, and bioprostheses. Key parameters of the heart were measured in classical echocardiographic projections (end systolic area, end-diastolic area, end systolic volume, and end diastolic volume of ventricles, ventricular ejection fraction, atrial volume, and the ratio of ventricular to atrial volumes). The patients were examined 1–2 days prior to and following the surgery—before discharge, 6 months later, 1 year later, and then annually within next 5 years. The examination data were collected in one- and two-dimensional modes by using Philips EpiQ-7, iE33, HDI, Siemens Acuson, and HP Sonos 2500 diagnostic ultrasound machines equipped with 2.5 and 3.5 MHz transthoracic sensors. Results: A comprehensive study of structural geometric remodeling parameters of heart cavities in the context of acquired MVD allowed identifying new patterns in changes of the heart chambers geometry. These changes are reflected in the IRV, a digital indicator of the severity of cardiac pathological remodeling. Analysis of the dynamics of post-operative vs. pre-operative IRV-based remodeling data also showed that the index is highly sensible to the hemodynamic features of through-flows in various designs of prostheses. The IRV has a pronounced prognostic power and allows predicting the long-term outcome of surgical treatment with an accuracy of 82.35%. Conclusions: The IRV predictive accuracy formed the basis of the original classification of types of cardiac remodeling, which can assist both in determining the optimal timing for surgery, and in conjunction with other clinical diagnostic data, in predicting the long-term outcome of heart geometry restoration depending on the type of surgical correction. The IRV can be used in evaluation of the heart geometry for any cardiac pathology. It makes the approach to the analysis of pathological remodeling of the heart understandable, consistent, and universal, and also opens up opportunities for further expanding the diagnostic capabilities of radiology in cardiac surgery at all stages of the diagnostic process.

Right Minithoraсotomy as a Standard Approach for Mitral Valve Surgery


 Background. Minimally invasive mitral valve surgery provides many advantages for patients.
 The aim. To investigate and represent our own experience in minimally invasive mitral valve surgery, and to describe the operative technique.
 Materials and methods. The study was included 100 consecutive patients who underwent a minimally invasive mitral valve repair or replacement through the right lateral minithoracotomy from June 2017 to December 2019.
 Results. Mitral valve repair was performed in 87 patients (87%), and 13 patients (13%) were required mitral valve replacement. In 24 patients (24%), concomitant procedures were performed: tricuspid valve repair, atrial septal defect repair and left atrial myxomectomy. Ring anuloplasty was performed in all patients who underwent mitral valve repair. Additional methods of correction were used in accordance to the lesion anatomy: neochords implantation, cleft and leaflet perforation closure, leaflet resection, Alfieri (edge-to-edge) stitch, posterior leaflet plication. There was no in-hospital and 30-day mortality. Post-operative strokes were not reported. No wound complications were observed in the femoral cannulation area. The total length of stay in a hospital was 6 ± 1.46 (3–9) days. There were no cases of mitral valve insufficiency greater more than mild degree after mitral valve repair at the time of discharge.
 Conclusions. Minimally invasive mitral valve surgery can be performed as a routine standard approach, provides safe and effective correction of the mitral valve defects, allows excellent results of mitral valve repair and replacement in various abnormalities. Minimally invasive approach enables to perform a large number of reconstructive valve techniques and perform simultaneous correction of atrial septal defects, tricuspid valve repair and atrial neoplasm removal.