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.

Modeling of Acute Pulmonary Arterial Hypertension in Pigs Using a Stable Thromboxane A2 Analogue (U46619): Dose Adjustment and Assessment of Hemodynamic Reactions.

U46619, a synthetic analogue of thromboxane A2 was used for modeling acute stable and reversible pulmonary arterial hypertension. Administration of U46619 in high doses led to vascular collapse and inhibition of cardiac function. The doses of U46619 were empirically selected that allow attaining the target level of pulmonary hypertension without systemic hemodynamic disturbances. The possibility of attaining the target level of pulmonary hypertension and reversibility of changes after termination of U46619 infusion make this model attractive for evaluation of the efficiency of different therapeutic methods of treatment of pulmonary hypertension in large animals.

Association of myocardial and serum miRNA expression patterns with the presence and extent of coronary artery disease: A cross-sectional study.

BACKGROUND: MicroRNA (miRNAs) participate in the pathogenesis of coronary artery disease (CAD). OBJECTIVE: To evaluate the expressions of myocardial and serum miRNA-27а, miRNA-133а, and miRNA-203 in CAD patients. METHOD: This cross-sectional observational study comprised 100 subjects (60.9 ± 1.0 years; 67% men). The right atrial and serum expressions of miRNA-27a, miRNA -133a, and miRNA-203 in 80 patients referred for elective coronary artery bypass graft surgery (CABG) and 20 control patients scheduled for heart valve surgery were analyzed using real-time polymerase chain reaction. RESULTS: There was a positive correlation between the SYNTAX score I index and serum miRNA-203 expression level (r = 0.693; p < .001). Patients with ≥3 coronary artery lesions had significantly higher myocardial expressions of miRNA-27a, miRNA-133а, and miRNA-203 than patients with 1-2 vessel disease in the atrial myocardium (miRNA-27a: 234.62 ± 29.51 vs. 182.39 ± 19.62 relative expression unit (REU); miRNA-133а: 127.53 ± 13.41 vs. 111.35 ± 12.31 REU; and miRNA-203: 5.25 ± 0.96 vs. 4.71 ± 0.67 REU; р < 0.05); the same association was found for serum miRNA expressions (miRNA-27a: 11.41 ± 3.85 vs. 4.82 ± 1.82 REU; miRNA-133а: 8.42 ± 2.43 vs. 4.35 ± 1.23 REU; and miRNA-203: 145.71 ± 15.73 vs. 43.70 ± 9.67 REU; р < 0.05). The decision tree method established that the risk of multivessel lesions was increased five-fold if the miRNA-203 serum expression was >101.00 REU (OR, 5.90; 95% CI, 2.34-9.46; p < .001). CONCLUSIONS: Both myocardial and serum miRNA-27а, miRNA-133а, and miRNA-203 expressions are higher in CABG patients than in non-CAD subjects. The serum miRNA-203 expression level corresponds to myocardial expression and is strongly correlated with the extent of coronary atherosclerosis.

Perivascular Innervation of the Pulmonary Artery in Human and Swine: A Comparative Study for the Development of an Experimental Model of Denervation.

For studying the possibility of using catheter denervation of the pulmonary artery for the treatment of pulmonary hypertension, large animals, such as pigs, are more suitable, because the diameter of the pulmonary artery in this case allows manipulation of the ablation catheter. The study of the perivascular adipose tissue of the trunk and bifurcation of the pulmonary artery in humans and pigs revealed differences in the density and diameter of nerve fibers, but their depth did not differ. Immunohistochemical analysis with different markers of the autonomic nervous system receptors revealed similar receptor profile in human and pigs, though the expression of all studied markers in pigs was less pronounced than in humans. These findings attest to similarity of the innervation of the pulmonary arteries in humans and pigs under normal conditions.

[Reverse remodelling of the heart after atrial fibrillation ablation in patients with heart failure with reduced ejection fraction].

AIM: To evaluate the effect of atrial fibrillation (AF) catheter ablation (CA) on long-term freedom from AF and left heart reverse remodeling in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: There were 47 patients (mean age 53.3 ± 10 years, 39 males) enrolled into single-center observational study, with left ventricular ejection fraction (LVEF) <40 %. Patients underwent CA for AF refractory to antiarrhythmic drugs. Baseline clinical data and diagnostic tests results were obtained during personal visits and / or via secure telemedical services. Personal contact with evaluation of recurrence of AF and echocardiographic values was performed with 30 (64 %) patients. RESULTS: Paroxysmal AF was present in 12 (40 %) patients, persistent - in 18 (60 %). During mean follow-up of 3 years (0.5-6 years) redo ablation was performed in 9 patients (30 %) with average number of 1.3 procedures per patient. At 6 months 24 (80 %) patients were free from AF, at last follow-up - 16 (53 %). The mean time to first recurrence following CA was 15.6±13.3 months. Follow-up echocardiography revealed significant LVEF improvement (р<0,0001), reduction of left atrium size (р<0,0001), left ventricle end-diastolic volume (р<0,002) and left ventricle endsystolic volume (p<0,0001) and mitral regurgitation (р=0,001). CONCLUSION: AF CA in patients with HFrEF is associated with improvement in systolic function and left heart reverse remodeling. Durable long-term antiarrhythmic effect often requires repeated procedures.

[Interventional treatment in patients with myocarditis: Pro and Contra].

AIM: Ventricular tachyarrhythmias (VTs) are often encountered in patients with inflammatory heart diseases. VT can become lifethreatening in patients with myocarditis, and the management may vary in different types of myocarditis. Purpose of the study is to describe VT characteristics in patients with verified myocarditis, and to evaluate the efficacy and safety of VT management, when tailored to the type of myocarditis. MATERIALS AND METHODS: Study population comprised: 56 patients with morphologically verified myocarditis; 18 patients with primary cardiomyopathy (control group). All patients underwent full clinical evaluation, endomyocardial biopsy (including immunohistochemical analysis). Forty (54 %) patients underwent radiofrequency catheter ablation of VT. An implantable cardioverter-defibrillator (ICD) was inserted in 17 patients. RESULTS: There was no statistically significant difference between myocarditis and primary cardiomyopathy groups by demographic and echocardiographic data. In myocarditis group, nonsustained VT and/or frequent premature ventricular beats were seen in 59 % of patients; sustained VT in 12,5 % subjects, 1 patient had a history of ventricular fibrillation. VT ablation was associated with a significant decrease in VT recurrence (p=0,0009) during the follow-up period. Active myocarditis was associated with a higher VT recurrence rate (67 % in active vs. 19 % in borderline myocarditis). Among patients with ICD implantation, only one subject (with active myocarditis at admission) had life-threatening ventricular arrhythmia. CONCLUSION: In this selected group of patients with verified myocarditis and clinically significant VTs, catheter ablation seems at least partly effective. Patients with borderline myocarditis and symptomatic VTs may benefit from ablation. Therefore, morphological diagnostic of myocarditis can be a key point in choice of treatment.