Effect of Levosimendan on miRNAs Regulation in the Failing Hearts
Status:
Recruiting
Trial end date:
2022-06-30
Target enrollment:
Participant gender:
Summary
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.