Aortic stenosis (AS) is the most commonly diagnosed valvular heart disease, and its prevalence increases with the aging of the general population. However, AS is often diagnosed at a severe stage, necessitating surgical treatment, due to its long asymptomatic period. The objective of this study was to analyze the frequency of AS in a population of cardiovascular patients using echocardiography (ECHO) and to identify clinical factors and features associated with these patient groups. We utilized machine learning methods to analyze 84,851 echocardiograms performed between 2010 and 2018 at the National Medical Research Center named after V.A. Almazov. The primary indications for ECHO were coronary artery disease (CAD) and hypertension (HP), accounting for 33.5% and 14.2% of the cases, respectively. The frequency of AS was found to be 13.26% among the patients (n = 11,252). Within our study, 1544 patients had a bicuspid aortic valve (BAV), while 83,316 patients had a tricuspid aortic valve (TAV). BAV patients were observed to be younger compared to TAV patients. AS was more prevalent in the BAV group (59%) compared to the TAV group (12%), with a p-value of <0.0001. By employing a machine learning algorithm, we randomly identified significant features present in AS patients, including age, hypertension (HP), aortic regurgitation (AR), ascending aortic dilatation (AscAD), and BAV. These findings could serve as additional indications for earlier observation and more frequent ECHO in specific patient groups for the earlier detection of developing AS.

The NOTCH-signaling pathway is responsible for intercellular interactions and cell fate commitment. Recently, NOTCH pathway genes were demonstrated to play an important role in aortic valve development, leading to an increased calcified aortic valve disease (CAVD) later in life. Here, we further investigate the association between genetic variants in the NOTCH pathway genes and aortic stenosis in a case–control study of 90 CAVD cases and 4723 controls using target panel sequencing of full-length 20 genes from a NOTCH-related pathway (DVL2, DTX2, MFNG, NUMBL, LFNG, DVL1, DTX4, APH1A, DTX1, APH1B, NOTCH1, ADAM17, DVL3, NCSTN, DTX3L, ILK, RFNG, DTX3, NOTCH4, PSENEN). We identified a common intronic variant in NOTCH1, protecting against CAVD development (rs3812603), as well as several rare and unique new variants in NOTCH-pathway genes (DTX4, NOTCH1, DTX1, DVL2, NOTCH1, DTX3L, DVL3), with a prominent effect of the protein structure and function.

Background: Aortic stenosis (AS) is a prevalent acquired heart valve disease with increasing incidence, particularly among older adults. Gender-specific differences in AS presentation, comorbidities, and outcomes remain underexplored, necessitating further investigation to optimize personalized treatment strategies. Objective: To evaluate the clinical and demographic characteristics, comorbidities, and survival outcomes of patients with AS, stratified by gender and aortic valve morphology. Methods: A retrospective analysis of 145,454 echocardiographic examinations (2009–2018) at the Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” identified 84,851 patients meeting the inclusion criteria (Vmax ≥ 2.0 m/s, age ≥ 18 years). Patients were stratified by gender and valve morphology (bicuspid aortic valve [BAV] vs. tricuspid aortic valve [TAV]). Survival was assessed in 475 pts with AS over a 16-year period (2009–2025) using Kaplan–Meier analysis. Statistical comparisons utilized STATISTICA v. 10.0, with p-values derived from P-tests. Results: Of the cohort, 4998 men and 6322 women had AS. Men with AS were older (median 64 vs. 57 years, p < 0.0001) and had higher systolic blood pressure (140 vs. 130 mmHg, p < 0.0001) than men without AS. Women with AS were also older (median 70 vs. 58 years, p < 0.0001) with higher systolic (140 vs. 130 mmHg, p < 0.0001) and diastolic blood pressure (80 vs. 80 mmHg, p < 0.0001). Men with AS had higher rates of hyperlipidemia (HLP) (26.3% vs. 10.3%, p < 0.0001), while women with AS had increased coronary artery disease (CAD) (35.7% vs. 26.4%, p < 0.0001), diabetes mellitus (DM) (13.4% vs. 10.2%, p < 0.0001), and obesity (10.9% vs. 10.2%, p = 0.06). Chronic heart failure (CHF) was more frequently reported in patients with AS, regardless of gender, compared to patients without AS (in men 53.4% vs. 41.8%, p < 0.0001; in women 54.5% vs. 37.5%, p < 0.0001). BAV was associated with higher AS prevalence (54.5% in men, 66.4% in women). Survival analysis revealed higher mortality. Over the 16-year follow-up period, the mortality rate was 21.7%. Conclusions: Mortality in a representative AS cohort reached 21.7%, underscoring the progressive nature of the disease and its long-term impact. Survival was negatively affected by age over 68.5 years, as well as the presence of aortic regurgitation (AR), increased peak aortic jet velocity, and enlarged maximum aortic diameter. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. Beta-blocker therapy in patients with varying degrees of aortic AS severity has not only demonstrated its safety but has also shown a positive effect on reducing mortality (improving survival). In contrast, the combination of angiotensin II receptor blockers (ARBs) with calcium channel blockers (CCBs) is quite dangerous for patients with AS and reduces their survival. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. In contrast, the absence of fibrinolytic therapy and anticoagulant treatment is associated with an improved prognosis. Conversely, the administration of antiarrhythmic agents and statins is correlated with enhanced survival outcomes, potentially attributable to their influence on coexisting comorbidities. Further research is required to delineate their precise mechanisms and contributions. These results emphasize the importance of early identification, comprehensive risk assessment, and individualized management strategies in improving outcomes for patients with AS.

Purpose: to evaluate the features of the course of complications in patients with BAV based on the results of a pathomorphological study.Material and methods: a retrospective analysis of a register of 328 patients with AS and dilation of the ascending aorta (DAA), based on histological studies performed in 2010–2022 was carried out. 209 patients were diagnosed with BAV as a result of histological examination, and 119 patients were diagnosed with tricuspid aortic valve (TAV). The type of BAV was analyzed in 139 operated patients based on the results of the analysis of surgical protocols.Results: according to the obtained results, the first type with fusion of the right and left coronary cusps prevailed among patients with BAV (78%), the smallest number of patients with BAV was with fusion of the right coronary and non-coronary cusps of the aortic valve (4%), while fusion of the left coronary with the non-coronary cusps of the aortic valve (AV) and patients with "true" BAV occurred in each case in 9% of patients. The formation of AS (75.6%), DAA (68.4%), and the combination of AS+DAA (81%) was more observed in the group of patients with the first type of BAV. According to the results of histology of the AV, there were no significant differences depending on the morphology of the valve. In particular, according to the results of AV histology, the frequency of calcification did not differ in groups of patients with BAV and TAV. Fibrosis with erasing of the layered histoarchitectonics of the AV of varying severity was detected in every second patient, regardless of the presence of congenital heart disease (CHD). According to the results of aortic histology, hemodynamic aneurysm in patients with BAV was much more common than in patients with TAV (p=0.0027). In addition, it was verified that in 39 patients out of 40 without pathomorphological changes in the aortic wall, aortic stenosis appeared in the diagnosis, of which 80% of patients had CHD: BAV. It was verified that 39 out of 40 patients without pathomorphological changes in the aortic wall had aortic stenosis in the diagnosis. Moreover, in 80% of patients, the main cause of aortic dilatation was identified as BAV.Conclusions: the results of this study demonstrated that in the vast majority of cases, aortic dilatation and aortic stenosis are formed during fusion of the right and left coronary cusps. The absence of morphological changes in the aortic wall in almost every third patient with DAA and BAV, confirms the genetic contribution to the formation of aortic dilatation in this category of patients and requires further study.