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.

[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.

Associations between ambient ozone, hydrocarbons, and childhood wheezy episodes: a prospective observational study in south east London.

OBJECTIVES: To explore the hypothesis that hydrocarbon species and other air pollutants which accumulate at low and high concentrations of ozone are more directly associated with childhood wheezy episodes than ozone. METHODS: Prospective observational study over 1 year set in the Lewisham district of south east London. The daily attendance rate of children with acute wheeze at the accident and emergency department of Lewisham Hospital was related to local measurements of ozone, hydrocarbon species, nitrogen dioxide (NO2), sulphur dioxide (SO2) and small particulate matter with diameter < 10 microns (PM10). RESULTS: An inverse relation was found between the air pollutants and ozone. After seasonal and meteorological adjustment a non-linear U shaped trend was found between incidence of wheeze and ozone. The trend was significant in children < 2 years of age but not in older children. In the younger age group, after adjustment for season, temperature, wind speed, and respiratory infection, the incidence relative to that at the mean daily ozone concentration of 32.7 micrograms/m3, was estimated to increase by 65% (95% confidence interval (95% CI) 22% to 122%) at an ozone concentration of 5 micrograms/m3 (1.5 SDs below the mean) and by 63% (95% CI -6% to 184%) at 80 micrograms/m3 (2.5 SDs above the mean). For several hydrocarbons there were significant positive linear relations found, again in children < 2 years of age but not older children. For benzene, the incidence increased by 8% (95% CI 2 to 13%) per SD (SD 2.8 micrograms/m3) increase in benzene concentration. A same day association between incidence and ozone was found to be the most significant but for other pollutants a lag of 2 days gave the most significant associations. No significant association was found for the non-hydrocarbon pollutants including SO2, NO2, and PM10. CONCLUSIONS: A U shaped relation was found between ozone and the incidence of wheezy episodes in young children. Certain hydrocarbon pollutants accumulate in the atmosphere when ozone concentrations are low, and are associated with childhood wheezy episodes. However, the U shaped association of ozone on incidence cannot be explained by these other pollutants. The finding supports an earlier finding that incidences of wheeze are at a minimum when ozone concentrations are 30-40 micrograms/m3.