Influence of standard heart failure therapy on readmission rate: opportunities and limitations in modern clinical practice

This review considers the clinical and epidemiological significance of hospitalizations for decompensated heart failure, as well as using it as an indicator of therapy effectiveness. The data on the frequency of using medications that reduce the hospitalization risk in randomized clinical trials and in real practice are presented. The reasons for inadequate prescription of drugs for the treatment of heart failure with reduced ejection fraction and their use in insufficient doses, which include therapeutic inertness and physiological limitations, as well as the need to introduce drugs with alternative mechanisms of action into clinical practice, are iscussed.

Combined Effect of Walking and Vitamin D Intake on Patients with Heart Failure

Objective: Patients with heart failure may benefit from vitamin D treatment, according to new research (Congestive Heart Failure). Methods: In our current nonrandomized clinical research, 43 individuals with dilated cardiomyopathy who did not exhibit substantial gains in physical functioning with optimum heart failure therapy were included. Twelve weeks of weekly vitamin D supplements (200,000 IU) were added to the heart failure therapy to help improve the patient's condition. On the other hand, researchers looked at how it affected the 6-minute walk distance and pro-BNP levels. To analyses the data, we utilized SPSS version 19. Accordingly, we utilized random samples t-tests to assess the substantial role of vitamin D supplementation on pre-intervention vitamin D level, 6-minute walk distance, and pro-BNP level, respectively. Significance was defined as an alpha value less than 0.01. Results: Individuals in NYHA class II (66%) were the majority, while those in NYHA classes I, III and IV were represented by 18%, 8% and 5%, accordingly. Following 14 weeks of vitamin D treatment, the group's mean vitamin D level was increased from 17.596.57ng/ml at baseline to 32.974.65ng/ml (p0.0006). Pre-intervention mean distance travelled was 806382ft, however after the intervention it rose to 945392ft (p-value 0.07). While before the intervention, the mean per-BNP level of research participant was 1025-636, and after intervention, it had enhanced to 160-80--a statistically significant improvement (p=0.005). Conclusion: According to a decline in blood pro-BNP characterized by an increase in six-minute walk distance, vitamin D administration decreases the intensity of heart failure.

The myosin activator: is another step forward in heart failure therapy?

Selective cardiac myosin activators constitute a new class of drugs capable of increasing cardiac contractility independently of intracellular calcium concentrations. In the GALACTIC-HF study, the first of this class of molecules, omecamtiv mercabil, was compared with the standard of care according to current guidelines, showing a significant reduction in the composite endpoint of first episode of heart failure or mortality due to cardiovascular causes in patients exposed to treatment compared with placebo. In particular, the effect was more pronounced for decreasing ejection fraction values, suggesting a potential further benefit of selective cardiac myosin activators in this category of patients.

Abstract P362: Gata4 Dimerization May Be A Target For Heart Failure Therapy

Introduction: Cardiac hypertrophy is regulated by activation of GATA4. Although GATA4 post-translational modification such as acetylation by p300 is well examined, the details of the activation mechanism of GATA4 are still unclear. The purpose of this study is to investigate whether GATA4 dimerization involved in transcriptional activation and cardiomyocyte hypertrophic responses. Methods and Results: A GST pull-down assay using GST fusion GATA4 full-length and deletion mutants demonstrated that GATA4 308-326, including the acetylation site, was required for the dimerization of GATA4. A DNA pull down assay showed that the C-zinc finger motif (256-295) and the acetylation site were required for the DNA binding capacity of GATA4. IP-WB using nuclear extract from HEK293T cells expressing FLAG- or HA-tagged GATA4 showed that co-expression of p300 increased the formation of the homo-dimer as well as acetylation of GATA4. The GATA4 homo-dimer was disrupted by both acetyl-deficient GATA4 and HAT-deficient p300. This result indicates that acetylation of GATA4 is important for dimerization of GATA4. Overexpression of the deletion mutant containing a GATA4 308-326 (G4D) prevented p300-induced GATA4 dimerization but not the p300 binding nor acetylation of GATA4. ChIP assay and DNA pulldown assay showed that G4D did not inhibit the p300-induced DNA binding of GATA4. In cardiomyocytes, the G4D inhibited phenylephrine-induced ANF and ET-1 promoter activities and cardiomyocyte hypertrophy. To perform the X-ray crystal structure analysis, recombinant GATA4 fragment including GATA4 308-326 was highly purified. The X-ray diffraction data of obtained crystals was collected. Resolution of the crystal was 3.1Å, which was insufficient for phase determine. To obtain a high-quality crystal, GATA4 fragment was crystallized in international space station, in collaboration with JAXA. Resolution of the crystal was 3.16Å, which was similar to the best data before obtained. Conclusions: These results suggest that GATA4 dimerization may play an important role in hypertrophy-response gene transcription. It is expected to elucidate the GATA4 dimerization mechanism and targeted this dimerization will lead to the development of a noble heart failure therapy.