Effect of Levosimendan on miRNAs Regulation in the Failing Hearts

Overview

Chronic heart failure is the terminal stage of various cardiovascular diseases. It is characterized with high fatality rate and high recurrence rate, which brings a heavy economic burden to patients and society. Although in recent years, the long-term prognosis of patients with heart failure has been greatly improved by the advances in drugs and new techniques, some patients have eventually progressed to refractory heart failure. The newly developed positive inotropic drug levosimendan is a new type of calcium sensitizer, increasing the sensitivity of troponin to calcium ions, without directly increasing the concentration of calcium ions in cardiomyocytes. Levosimendan improves heart function by increasing myocardial contractility, dilating blood vessels, regulating coronary blood flow, and also exhibits anti-inflammatory, anti-oxidant and anti-apoptotic effects. Compared with traditional inotropic drugs, levosimendan does not increase calcium ion concentration or increase oxygen consumption. And it does not easily lead to malignant arrhythmia or increase the long-term mortality of patients. Because of its long half-life, intermittent use of levosimendan can improve contractile function for a long time, thereby effectively alleviating the symptoms of patients with advanced heart failure. Patients treated with levosimendan had a higher survival rate, fewer hospitalizations, and a greatly improved quality of life. MicroRNAs (miRNAs) are a class of non-coding RNAs with important regulatory roles. They are 22-nucleotide single-stranded RNAs derived from endogenous hairpin structure transcripts. MiRNAs are reported to be involved in the pathological process of heart remodeling. MiRNAs can be secreted by cells into the peripheral blood and exist stably, which can be used as new diagnostic markers for various diseases. The investigators have previously conducted simultaneous detection of miRNAs in myocardial tissue and peripheral blood in patients with heart failure, and conducted an epidemiological follow-up study. The investigators have identified three cardiac-specific secretory miRNAs (miR-660-3p, miR-665 and miR-1285-3p) which are significantly up-regulated in the plasma of patients with chronic heart failure. Subsequent analysis proved them as valuable biomarkers for the diagnosis and prognosis of heart failure. The investigators hypothesis that the new positive inotropic drug levosimendan improve heart function by regulating the miRNAs in patients with heart failure. This study aims to treat patients with advanced heart failure with levosimendan. By combining the expression of myocardial specific miRNAs, myocardial injury markers, hemodynamics, patient symptoms, long-term prognosis and other clinical indicators, the investigators will explore the relationship between the three myocardial-specific miRNAs expression and cardiac function improvement by levosimendan treatment.