Molecular effects of cardiac contractility modulation in patients with heart failure of ischemic aetiology uncovered by transcriptome analysis.

Cardiac contractility modulation (CCM) is based on electrical stimulation of the heart without alteration of action potential and mechanical activation, the data on its fundamental molecular mechanisms are limited. Here we demonstrate clinical and physiological effect of 12 months CCM in 29 patients along with transcriptomic molecular data. Based on the CCM effect the patients were divided into two groups: responders (n = 13) and non-responders (n = 16). RNA-seq data were collected for 6 patients before and after CCM including 3 responders and 3 non-responders. The overall effect of CCM on gene expression was mainly provided by samples from the responder group and included the upregulation of the genes involved in the maintenance of proteostasis and mitochondrial structure and function. Using pathway enrichment analysis, we found that baseline myocardial tissue samples from responder group were characterized by upregulation of mitochondrial matrix-related genes, Z disc-protein encoding genes and muscle contraction-related genes. In summary, twelve months of ССM led to changes in signaling pathways associated with cellular respiration, apoptosis, and autophagy. The pattern of myocardial remodeling after CCM is associated with initial expression level of myocardial contractile proteins, adaptation reserves associated with mitochondria and low expression level of inflammatory molecules.

Type 2 Diabetes Mellitus and Chronic Heart Failure with Midrange and Preserved Ejection Fraction: A Focus on Serum Biomarkers of Fibrosis.

As myocardial fibrosis might be an important contributor to the association of diabetes mellitus with left ventricular (LV) dysfunction and chronic heart failure (HF), we investigated the profile of some proinflammatory, profibrotic biomarkers in patients with type 2 diabetes mellitus (T2DM) at various stages of the cardiovascular disease continuum from absence of clinic since and symptoms to HF with preserved (HFpEF) and midrange ejection fraction (HFmrEF). Material and Methods. Sixty-two patients with T2DM (age 60 [55; 61]), 20 patients without clinical manifestations of HF and 2 groups with clinical manifestations of stable HF, 29 patients with HFpEF, and 13 patients with HFmrEF, were included in the study. The control group consisted of 13 healthy subjects and normal BMI. All patients underwent transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), highly sensitive C-reactive protein (hsCRP), soluble suppression of tumorigenesis-2 (sST2), galectin-3, C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1). Results. Patients with HFmrEF had higher values of LV volumetric parameters, indexed parameters of LV myocardial mass (LVMM), and higher concentrations of Nt-proBNP (all p < 0.05). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF (p = 0.01 and p = 0.03, respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF (p = 0.043 and p = 0.033, respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area (r = -0.58, p = 0.001), PIIINP, TIMP-1, and LV end-diastolic volume (r = -0.68 and p = 0.042 and r = 0.38 and p = 0.02, respectively). Conclusion. The dynamics at various stages of the cardiovascular disease continuum in the serum fibrosis markers may reflect an increase in fibrotic and decrease in antifibrotic processes already at the preclinical stage of HF. At the same time, the changes found in the circulating procollagen levels may indicate a shift in balance towards type I collagen synthesis in HFmrEF compared with HFpEF.

[Results of 3 years work of the Russian hospital register of chronic heart failure (RUssian hoSpital Heart Failure Registry - RUS-HFR): relationship between management and outcomes in patients with chronic heart failure].

AIM: To analyze management and outcomes in patients with CHF managed by specialists in heart failure (HF) or general cardiologists/physicians in real-life clinical practice. MATERIALS AND METHODS: Survival rate, rehospitalization rate, general health condition, and the administered therapy were evaluated for HF patients with reduced LV ejection fraction at three years of discharge from cardiological hospitals. These patients had been included in a prospective, multicenter, observational study, "The Russian Hospital HF Registry" (RUS-HFR). The first group consisted of patients who were managed at a specialized HF department of the Federal Center and followed up at the outpatient stage by a cardiologist specializing in HF (Group 1, St.­Petersburg; n =74). The other two groups (Group 2 and Group 3) included patients who were managed at other cardiological departments of the Federal Center (n=186) or the Regional Center (n=130) and subsequently followed up at the place of residence. RESULTS: After the discharge from the hospital, 58-95 and 12-19% of RUS-HFR patients were followed up by a cardiologist or a physician, respectively, on an outpatient basis while 5-23% of patients did not visit a doctor at all. In three years, the survival rate of Group 1, 2, and 3 patients was 80 vs. 78 (р>0.05) vs. 52% (р0.05) vs. 100% (p1,2.

[Results of Russian Hospital Chronic Heart Failure Registry in Three Subjects of Russian Federation].

Aim of the RUssian hoSpital Heart Failure Registry (RUS-HFR) was to analyze clinical and epidemiological characteristics, application of modern drug and non-drug therapy among hospitalized patients with systolic chronic heart failure (CHF) in 3 subjects of Russian Federation. MATERIAL AND METHODS: We conducted a prospective multicenter observational study in 3 cardiological centers (Petersburg, Orenburg, Samara) in which we recruited patients aged 18-75 years with left ventricular ejection fraction less or equal 40% without ongoing myocardial infarction or pulmonary thromboembolism. RESULTS: Between October 2012 and June 2014 we included 524 patients (mean age 60 years, >79% men) mostly with NYHA class III CHF. Main etiological factors were ischemic heart disease and arterial hypertension, which was not corrected by the time of admission in 20-40.7% of patients. Portions of patients who had undergo the myocardial revascularization, surgery because of valvular heart defects, and implantation of permanent pacemaker including device for cardiac resynchronizing therapy were 11-41, 0-4, and 0-19.5%, respectively. In up to 25% of patients therapy with one of main medications or diuretic was initiated after hospitalization. At discharge 82.3-8.3, 76.3-95.8, 65.9-81.1, 80.7-94.6% of patients received ACEI/ARB, -adrenoblockers, MRA, diuretic therapy, respectively. Implantation of cardioverter ICD/CRT, ICD and heart transplantation were considered indicated in 0-21.2 and 0-6.6% of patients, respectively. Duration of hospitalization was 26+/-14, 15+/-10, and 13+/-5 bed-days in Petersburg, Orenburg, and Samara, respectively. CONCLUSIONS: Compared with data obtained 10 years earlier portrait of a patient with in general remained unchanged. However portion of patients who had undergone cardio-surgical and electrophysiological interventions became tangible, and numbers of patients receiving therapy with ACEI/ARB, -adrenoblockers, and MRA became comparable with those in European registries. Significant deviations from guidelines on drug therapy were revealed at prehospital stage; and high-technology methods of therapy were insufficiently often recommended in participating hospitals. Portion of hospitalizations not related to acute decompensation was 5-37%, while duration of such hospitalizations as well as hospitalizations because of acute decompensation of CHF significantly exceeded this parameter in EU and USA. Absence of obligatory drug therapy prior to admission in a part of patients in RUS-HF raises questions on correction of patients compliance and on creation of a system of specialized ambulatory surveillance of CHF patients after discharge from hospital.