Relevant aspects of the pathogenesis, diagnosis, And treatment of heart failure with preserved LV EF
This review analyzes results of studies of the recent decade that focus on epidemiology, mechanisms of development, diagnostic methods, and treatments of heart failure with preserved ejection fraction (HFpEF). As expected, the prevalence of HFpEF continues to increase due to the growing contribution of comorbidities to the structure of causes for chronic heart failure (CHF), such as arterial hypertension with left ventricular hypertrophy, obesity, chronic kidney disease, as well as due to ageing of the population and decreased contributions of ischemic heart disease and myocardial infarction. Concomitant diseases are a source of low-intensity microvascular inflammation, which is currently assigned a role of a trigger mechanism eventually provoking energy deficiency, disorders of cardiomyocyte relaxation, and diffuse myocardial fibrosis. Both these processes lead to increased heart muscle rigidity and abnormally high left ventricular filling pressure (LVFP). High LVFP is associated with the development of pulmonary venous congestion and impairment of alveolar blood oxygenation, which form the clinical picture of HFpEF. Detecting high LVEF with tissue Doppler echocardiography by the E / e’ value became the instrumental basis for the HFpEF diagnostics. Recognition of inflammation and fibrosis as the key pathogenetic factors marked the main vector of modern therapy for HFpEF (anti-inflammatory and antifibrotic). The best implementation of this vector became possible with the advent of drugs from the class of angiotensin receptor and neprilysin inhibitors (ARNI), sodium-glucose cotransporter type 2 (SGLT2) inhibitors, and aldosterone antagonists. However, the efficacy of such treatments is evident only with the LV EF <60-65% while at higher values, the efficacy substantially decreases. This limitation may result from the heterogenous nature of the disease and requires more advanced methods for verification of HFpEF clinical phenotypes. Among such methods, transcriptomic, metabolomic, and proteomic approaches are considered. With the use of capabilities of the “machine learning” and the artificial intelligence, these approaches can become a new frontier in research to represent an important step towards personalized medicine for patients with HFpEF.

Aim      To determine the incidence rate and the practical significance of right ventricular dysfunction (RVD) in the development of cardiovascular complications in patients with decompensated chronic heart failure (DCHF).

Material and methods  This prospective, single-site observational study included 171 patients older than 18 years with NYHA functional class (FC) II-IV chronic heart failure (CHF) who were hospitalized for DCHF. Standard and extended 2D and 3D echocardiography (EchoCG) was performed for all patients on admission. Additionally, functional characteristics of the right ventricle (RV) were evaluated in the 3D mode followed by autonomic 3D processing with a EchoPac station (USA). RVD was taken as a disorder of two or more RV functional parameters according to results of 2D EchoCG, or a reduced RV free wall strain according to results of 2D speckle-tracking EchoCG, or a reduced RV ejection fraction (EF) according to results of 3D EchoCG. Statistical analysis was performed with a SPSS Statistics v. 26.0 software.

Results The incidence rate of RVD in general population of patients with DCHF was 75.4 % (n=129). A higher prevalence of RVD was observed in patients with CHF with a low left ventricular (LV) EF (90.1 %). Patients with RVD had a more severe clinical status (significantly higher FC and higher Clinical Condition Scale (CCS) scores), more frequent atrial fibrillation (AF), and higher concentrations of uric acid and total bilirubin. RVD significantly correlated with male sex (odds ratio (OR), 2.05; 95 % confidence interval (CI), 1.01–4.19; р=0.046) and AF (OR, 3.52; 95 % CI, 1.71–7.26; р<0.001). Patients with RVD had lower values of both LV and RV function. Lower LV EF and AF increased the probability of RVD by 1.06 times (95 % CI, 0.90–0.98; р=0.001) and by 2.63 times (95 % CI, 1.08–6.40; р=0.001), respectively. Evaluation of the predictive significance of RV parameters measured by 2D and 3D EchoCG showed only effects of RV EF (2D) and RV global longitudinal strain (GLS) (3D) on all-cause hospitalization. RVD as evaluated by accepted criteria did not influence adverse outcomes.

Conclusion      The determined incidence, correlations, and the predictive value of RVD in patients with DCHF indicated the appropriateness of assessing the RV function to optimize the management of patients regardless of the CHF phenotype.

Aim      To evaluate the endothelial function using an Endo-PAT2000 instrument before and after mental stress tests in patients with Tacotsubo syndrome (TS) during acute and long-term periods and to compare the obtained results with laboratory markers of endothelial dysfunction (ED).

Material and methods  This study included 45 patients with TS (mean age, 63.5±13.7 years) and 40 healthy volunteers (control group, CG). All patients of the main group during the acute period (first 7–14 days) and long-term period (at 1 and 2 years), as well as CG subjects, underwent evaluation of the endothelial function with an Endo-PAT 2000 instrument, and the reactive hyperemia index (RHI) was determined before and after mental stress tests. Also, concentrations of endothelin 1 (ET-1) and numbers of circulating endothelial cells (CEC) were measured after a two-year follow-up of TS patients.

Results During the acute period of disease, all TS patients (n=45) had ED: RHI was below the threshold level of 1.67; furthermore, 42 (93.3 %) patients retained a lower RHI following mental stress. At one year (n=40), 16 (40%) patients showed ED at rest along with a significantly increased mean RHI. Mental stress produced at one year was associated with ED in 28 (70 %) TS patients. At two years (n=44), resting RHI was lower than normal in 19 (43.2 %) patients. Mental stress tests performed at two years were associated with ED in 29 (65.9 %) patients (RHI ≤1.67). Only 10% of CG subjects had a lower-than-normal RHI, which was significantly less than in the main group of TS patients during the acute and long-term periods (p<0.05). Mean values of laboratory markers for ED also were significantly different between TS patients during the long-term period of disease (n=41) and CG subjects (n=40; p<0.01).

Conclusion      During acute and long-term periods of disease, most of TS patients had impaired vascular reactivity both at rest and during mental stress. The laboratory markers of ED, ET-1 and CEC can be used in clinical practice for evaluation of the risk for TS.

Aim      To determine specific clinical characteristics caused by a combination of the rs397516037 pathogenic variant in the myosin-binding protein C (MTBPC3) and the rs749628307 polymorphic variant in the vinculin (VCL) gene in a Russian family of carriers and to evaluate the contribution of the rs749628307 polymorphic variant in the VCL gene to the development of hypertrophic cardiomyopathy (HCMP).

Material and methods  The family under study included one healthy person and 3 patients with HCMP. A targeted analysis of proband’s exome was performed. A structural alignment for both forms of the VCL protein, the canonical form and the form with p.Arg230His substitution, was performed.

Results The pathogenic rs397516037 variant and the potentially pathogenic rs749628307 variant were detected in the proband and several family members. A possibly damaging variant rs749628307 was detected in the proband and several family members evaluated in this study. The structural alignment confirmed that the rs749628307 variant did not alter the protein structure significantly and could not cause an impairment or loss of the protein function.

Conclusion      This study demonstrated that apparently the rs749628307 variant in the VCL gene does not affect the protein structure in a pathogenetically significant way, neither does it affect the severity and form of the clinical manifestations of HCMP; therefore, it cannot be considered as pathogenic.

Aim      To evaluate a possibility of using radiofrequency catheter ablation guided by intracardiac echocardiography (ICE), its efficacy and safety for treatment of ventricular tachycardia (VT) of various etiology.

Material and methods  Catheter intervention was performed for 20 enrolled patients with symptomatic VT. Ablation procedures were guided by a 3D electroanatomical mapping system and ICE.

Results Mean duration of the procedure was 201.2±62.5 min. The procedure was successful (non-inducibility of VT) in 100% of cases. None of the patients had postoperative complications.

Conclusion      Ablation of VT arrhythmogenic substrate guided by 3D electroanatomical navigational mapping and ICE without X-ray is feasible and safe.

Aim      To determine the effect of minimally invasive interventions on the quality of life (QoL), pain syndrome, and cosmetic effect in patients with a pathology of chest aorta as compared with a group of traditional access.

Material and methods  From 2016 through 2020, 77 of 226 (34%) patients with an aneurysm in the proximal chest aorta and mini-sternotomy were prospectively selected starting from 2017. To evaluate differences between the effects of mini-sternotomy and the traditional access on QoL and pain syndrome a control group of patients with full sternotomy (n=77) was formed using pseudorandomization. Intergroup comparison of QoL, pain syndrome, and cosmetic parameters was performed at various time points.

Results Mini-sternotomy provided a decrease in pain syndrome both during the early period (day 3), and during movements upon discharge. Also, mini-sternotomy decreased the duration of stay in the hospital compared to full sternotomy (8.1±2.1 vs. 8.9±2.5 days, respectively; р>0.0331). A more frequent use of analgesics by patients with full sternotomy was noted. Mini-sternotomy was associated with a faster recovery of most QoL parameters according to the SF-36 questionnaire at one year after surgery. The questionnaire included summarizing parameters of physical and mental health components (Physical Health Component, Physical Health (PH): 54.3±11.9 vs. 58.2±8.2, respectively; p=0.046; Mental Health Component, Mental Health (MH): 53.8±6.8 vs. 57.8±9.5, respectively; p=0.013). In addition, patients with minimal access showed higher values of the cosmetic effect by a 5-score scale (4.08±0.8 vs. 4.39±0.8, respectively; p=0.049) and a greater interest to having a minimal access surgery.

Conclusion      Mini-sternotomy beneficially influences the pain syndrome, cosmetic outcome, and QoL and provides a shorter duration of rehabilitation and a sooner return to work and everyday life compared to full sternotomy.

Aim    To study platelet adhesion mediated by von Willebrand factor (VWF) in patients with premature ischemic heart disease (IHD).
Material and methods    This study enrolled 58 patients with stable IHD, including 45 men younger than 55 years with the first manifestation of IHD at the age of <50 years and 13 women younger than 65 years with the first manifestation of IHD at the age of <60 years. The control group consisted of 33 patients, 13 men younger than 55 years and 20 women younger than 65 years without IHD. Platelet adhesion to the collagen surface at the shear rate of 1300 s-1 was studied by evaluating the intensity of scattered laser light from the collagen-coated optical substrate in a flow chamber of a microfluidic device after 15-min circulation of whole blood in the chamber. Decreases in platelet adhesion after addition to the blood of monoclonal antibodies (mAb) to platelet receptors glycoproteins Ib (GPIb) to inhibit the receptor interaction with VWF were compared for patients of both groups. 
Results    In patients with premature IHD, the decrease in platelet adhesion following the platelet GPIb receptor inhibition was significantly less than in patients of the control group (74.8 % (55.6; 82.7) vs. 28.9 % (–9.8; 50,5), p <0.001). For the entire sample, the median decrease in platelet adhesion following the GPIb receptor inhibition was 62.8 % (52.2; 71.2). With an adjustment for traditional risk factors of IHD, a decrease in platelet adhesion of >62.8% after blocking GPIb receptors increased the likelihood of premature IHD (OR=9.84, 95 % CI: 2.80–34.59; p <0.001).
Conclusion    Blocking the interaction of GPIb receptors with VWF in patients with premature IHD and increased shear rate induced a greater decrease in platelet adhesion than in patients without this disease. This suggested that an excessive interaction of VWF with platelets might contribute to the pathogenesis of premature IHD.

Aim    The Naples prognostic score (NPS) simultaneously evaluates inflammation and malnutrition, which are two main factors that play a role in the pathophysiology and prognosis of heart failure (HF). In this study, we aimed to examine the relationship of NPS with in-hospital mortality of hospitalized patients with a diagnosis of HF.
Material and Methods    A total of 496 hospitalized HF patients included in this study. The patients were divided into two groups as deceased and living. The clinical and demographic characteristics of each patient were recorded. NPS of each patient was calculated.
Results    NPS was significantly higher in the deceased group compared to the living group (3.6±0.61, 3.21±0.97, respectively; p=0.003). According to multivariate regression analysis: NPS (OR: 1.546, 95 % CI: 1.027–2.327; p=0.037), systolic blood pressure (OR: 0.976, 95 % CI: 0.957–0.995; p=0.015), and white blood cell count (OR: 1.072, 95 % CI: 1.007–1142; p=0.03) are independent predictors for in-hospital mortality in HF patients.
Conclusion    This study demonstrated a strong correlation between NPS and mortality in HF. This new score can be used to predict the prognosis of HF as it shows both the level of inflammation and nutrition.

A qualitative change in the risk profile after an episode of decompensated heart failure (HF) calls for an as immediate as possible therapeutic response. In the absence of uniform guidelines for the sequence and timing of administering the background therapy during the hospitalization period and the subsequent “vulnerable” period, clinicians have to rely on available expert opinions and results of conducted studies. The article focuses on an evidence base for the use of background therapy for HF during the above-mentioned periods. Special attention is paid to the conditions and principles of initiating this therapy.

X-ray computed tomography coronary angiography (CTCA) is a current method for diagnosing ischemic heart disease. Although this method has a high specificity and a negative predictive value in diagnosing coronary obstructions, there are limitations in determining the hemodynamic significance of the stenosis. Extensive use of noninvasive methods for evaluation of coronary hemodynamics, specifically evaluation of the fractional flow reserve (FFR) is limited due to its high cost and risks of complications. Mathematical modeling of coronary circulation and its reserve based on CTCA data is an up-to-date method that has been experimentally confirmed and clinically validated. This method showed a high diagnostic efficacy in several large studies that used the invasive determination of FFR as a “gold standard”. This review addresses the current state of studies on mathematical modeling for fractional coronary reserve in patients with ischemic heart disease, as well as the limitations and prospects of this method.