Endothelial-Mesenchymal Transition or Functional Tissue Regeneration – Two Outcomes of Heart Remodeling

Heart remodeling occurs as a compensation mechanism for the massive loss of tissue during initial heart failure and the consequent inflammation process. During heart remodeling fibroblasts differentiate to myofibroblasts activate their secretion functions and produce elevated amounts, of extracellular matrix (ECM) proteins, mostly collagen, that form scar tissue and alter the normal degradation of ECM. Scar formation does replace the damaged tissue structurally; however, it impedes the normal contractive function of cardiomyocytes (CMs) and results in long-lasting effects after heart failure. Besides CMs and cardiac fibroblasts, endothelial cells (ECs) and circulating endothelial progenitor cells (cEPCs) contribute to heart repair. This review summarizes the current knowledge of EC-CM crosstalk in cardiac fibrosis (CF), the role of cEPCs in heart regeneration and the contribution of Endothelial-mesenchymal transition (EndoMT).

Functional tricuspid regurgitation, related right heart remodeling, and available treatment options: good news for patients with heart failure?

Significant functional tricuspid regurgitation (FTR) represents a poor prognostic factor independent of right ventricular (RV) function. It is usually the consequence of left-sided cardiac diseases that induce RV dilatation and dysfunction, but it can also resulted from right atrial (RA) enlargement and consequent tricuspid annular dilatation. FTR is very frequent among patients with heart failure, particularly in those with reduced LVEF and concomitant functional mitral regurgitation. The development of three-dimensional echocardiography enabled detailed assessment of tricuspid valve anatomy, subvavlular apparatus, and RA and RV changes, as well as accurate evaluation of FTR etiology. Due to high in-hospital mortality risk in patients who were operatively treated for isolated FTR, it has been treated only medically for a long time. Percutaneous approach considers mainly transcatheter tricuspid valve repair (edge-to-edge and annuloplasty) and represents a very attractive option for the high-risk patients. Studies that investigated the effects of different devices showed excellent feasibility and safety, followed by significant reduction in FTR grade, improvement in functional capacity and NYHA class, quality of life, and reduction in hospitalization due to heart failure. Some investigations also reported a decreased mortality in FTR patients. Nevertheless, the results of these investigations should be interpreted with cautious due to the small number of participants and relatively short follow-up. The aim of this review was to summarize the existing data about the clinical importance of FTR and FTR-induced right heart remodeling and currently existing therapeutic approaches for treatment of FTR.

Intestinal Microbial-tissue Complex and Chronic Heart Failure (part 1): Pathogenesis

Antigenic and metabolic integration of the intestinal microbiota into the homeostasis of the human body is a factor that claims to play a key role in the pathogenesis of cardiovascular diseases. It acquires special significance against the background of the decrease in blood circulation and congestion in the digestive system during chronic heart failure. Aim of the review is analysis and synthesis of studies results on the role of intestinal microbiocenosis in the pathogenesis of heart remodeling and chronic heart failure. The search for articles was conducted in databases eLIBRARY.RU and Medline for the key terms "gut microbiota (microbiome, microbiocenosis)", "dysbiosis (dysbacteriosis)", "excessive bacterial growth syndrome", "lipopolysaccharide (endotoxin)", "trimethylamine-N-oxide" in combination with the terms "heart failure", "myocardial remodeling", "myocardium" in Russian and English, respectively. We selected articles containing the results of clinical and experimental studies published from 1995 to 2020. Review articles were considered only on the subject of the cited original publications. Most researchers have established the relationship between chronic heart failure and dysfunction and changes in the qualitative and quantitative composition of intestinal microbiocenosis. As negative changes, it is customary to note the proliferation of gram-negative opportunistic bacteria with concomitant endotoxinemia and a decrease in the pool of commensal microbiota. The available data suggest that the participation of the intestinal microbial-tissue complex in the pathogenesis of chronic heart failure and heart remodeling is realized through the activation of a local and then systemic inflammatory response, accompanied by cardiodepressive action of pro-inflammatory cytokines and universal proliferation factors, an imbalance of matrix metalloproteinases and their inhibitors, the initiation of apoptosis, fibrosis, and loss of contractile myocardium. Besides, a decrease in the production of short-chain and polyunsaturated fatty acids and vitamins by the commensal microbiota may be associated with changes in the electrical properties of cardiomyocyte membranes, a decrease in the systolic function of the left ventricle of the heart, and an increase in the risk of sudden cardiac death. It's also shown that the direct cardiotoxic effect of microbial molecules (lipopolysaccharides, peptidoglycans, trimethylamine-N-oxide, etc.), which interact with the receptors of cardiomyocytes and microenvironment cells, can cause the development of myocardial remodeling and its dysfunction. Recent studies have established mechanisms of myocardial remodeling mediated by microbial molecules, which may be associated with new strategies for the treatment and prevention of heart failure.

The impact of chronic heart failure on heart remodeling in patients with atrial fibrillation

Atrial fibrillation (AF) and chronic heart failure (CHF) often coexist due to common pathophysiological mechanisms and risk factors. However, the effect of CHF on heart remodeling in patients with permanent AF has been insufficiently studied. The aim: to study the influence of CHF on changes in structural and geometric parameters and diastolic function of the heart in patients with permanent AF. Materials and methods. The study included 100 patients (men – 60 % (n = 60); women – 40 % (n = 40)) with CHF of ischemic origin and AF, stage II AB, NYHA II-IV FC, and 16 coronary heart disease patients (men – 62.5 % (n = 10), women – 37.5 % (n = 6)) with AF without signs of CHF. Patients were comparable in age (P = 0.267), height (p = 0.406), weight (P = 0.518), body surface area (P = 0.388). Doppler echocardiography was performed on the device Esaote MyLab Eight (Italy) according to standard methods. Results. Patients with AF and signs of CHF were dominated by individuals with eccentric hypertrophy (49 % vs. 19 %; P = 0.0270), and patients with AF without signs of CHF – with eccentric remodeling (0 % vs. 25 %; P = 0.0001). Patients with AF and signs of CHF had significantly higher systolic pressure in the pulmonary artery (54.85 ± 14.23 mm Hg vs. 42.99 ± 11.94 mm Hg; P = 0.028) and pulmonary capillary wedge pressure (PCWP) (12.18 (9.80; 15.33) mm Hg vs. 8.92 (7.62; 10.50) mm Hg; P = 0.005) than patients with AF without signs of CHF, indicating more pronounced pulmonary hypertension and a more significant increase in left atrium pressure. AF patients with signs of CHF demonstrated significantly higher left ventricle end-diastolic pressure (LVEDP), as evidenced by the parameters: E\E’ medial (9.87 ± 5.24 vs. 6.15 ± 1.39; P = 0.001), E/E’ mean (8.38 ± 4.21 vs. 6.06 ± 1.97; P = 0.005), e’ medial (9.96 ± 3.79 cm/s vs. 12.81 ± 3.60 cm/s; P = 0.004). AF patients with signs of CHF had decreased LV EF (55.58 ± 14.65 % vs. 65.44 ± 10.87 %; P = 0.006), systolic velocity of the medial fibrous ring of the mitral valve S (6.92 ± 2.41 cm/s vs. 8.40 ± 2.03 cm/s; P = 0.015), and significantly higher values of TEI RV (0.58 ± 0.16 c. u. vs. 0.48 ± 0.11 c. u.; P = 0.011), but decreased TAPSE values (16.22 ± 4.60 mm vs. 19.54 ± 5.00 mm; P = 0.067), indicating more pronounced systolic dysfunction of both ventricles. Conclusions. Comorbidity of CHF and AF in patients is accompanied by the increased percentage of eccentric hypertrophy (49 %; P = 0.027), more pronounced systolic dysfunction of the left and right ventricles, increased LVEDP, PCWP, systolic pressure in the pulmonary artery, dilation of the inferior vena cava.