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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 4, July/August 2020
AFRICA
199
Discussion
HF is a serious manifestation of various heart diseases and
represents the final stage. With the aging of the population in
China, the incidence of chronic diseases such as coronary heart
disease and hypertension is on the rise. Improvements in medical
treatment prolong the survival period of patients with heart
disease and eventually it develops into HF, which means a steady
increase in the prevalence of HF.
13
Acute decompensated HF
(ADHF) is an advanced stage of HF and it has a very serious
impact on the quality of life of patients.
Myocardial contractility was shown in one study to increase
because of increased sympathetic excitability and an activated
renin–angiotensin–aldosterone system in patients with ADHF.
14
Positive myodynamic agents used clinically can enhance
myocardial contractility, but their adverse reactions are serious,
and long-term use may even lead to an increase in mortality rate.
15
Levosimendan is an intracellular calcium sensitiser. The main
mechanisms of levosimendan in the treatment of ADHF are as
follows: (1) increasing the sensitivity of myocardial contractile
proteins to Ca
2+
and acting as a selective Ca
2+
sensitiser during
systole, thereby enhancing myocardial contractility and cardiac
output, but without affecting intracellular Ca
2+
concentration;
(2) activating ATP-sensitive K
+
channels on cell membranes to
exert vasodilation and reduce cardiac load; (3) producing an
anti-inflammatory and anti-oxidative stress response to reduce
neuroendocrine activation and endothelin-1 (ET-1) levels; (4)
selective inhibition of phosphodiesterase III at high doses is rare.
The half-life of the prototype drug is about one to 1.5
hours, and the active metabolites OR-1896 and OR-1855
are formed after acetylation in the liver. They have similar
effects to levosimendan, but the half-life is about 75 to 80
hours. Therefore, the haemodynamic effects of the prototype
drug can be maintained several days after discontinuation of
administration.
6,16-18
In addition, patients with ADHF have
a poor response to drugs, lack of response to treatment and
deterioration of multi-organ function, and require repeated
hospitalisation.
19
In our study, ADHF patients with significant
impairment of LVEF were selected as the subjects to observe the
short-term efficacy and safety of levosimendan.
The Chinese guidelines for the diagnosis and treatment
of heart failure
1
recommended NT-proBNP monitoring for
the diagnosis and treatment of acute and chronic HF. It is
an important indicator for evaluating the severity of HF.
1
NT-proBNP has no biological activity and its half-life is 60 to 120
minutes. By detecting NT-proBNP in patients with HF, clinicians
can roughly infer the severity of cardiac insufficiency, which is of
great significance for the diagnosis and treatment of HF.
20,21
Zhang
et al
. compared the efficacy of domestic levosimendan
and dobutamine in the treatment of ADHF, and concluded that
levosimendan could better reduce NT-proBNP level and improve
the heart function of patients with acute HF.
22
Other studies
have also shown that levosimendan combined with anti-heart
failure drugs was more effective than anti-heart failure drugs
alone in the treatment of refractory HF. While levosimendan
improved the symptoms of HF, NT-proBNP levels also
decreased significantly.
23
Similar results were shown in our study.
Compared with the control group treated with only conventional
HF drugs, NT-proBNP level decreased more significantly in the
experimental group treated with levosimendan.
LVEF refers to the percentage of stroke output to end-diastolic
volume, which is related to contractile state. It is a commonly
used index to reflect cardiac function and is widely used
in clinical diagnosis, treatment and research. NYHA cardiac
function classification is usually used to determine the severity of
HF symptoms, which is clearly related to survival rate.
1
Several studies have shown that levosimendan significantly
increased cardiac output, improved HF symptoms and reduced
mortality rates.
24-26
Wang
et al
. found that levosimendan
improved dyspnoea and systemic symptoms more significantly
than dobutamine in patients with severe decompensated HF.
27
In our study, the level of LVEF in both groups increased after
treatment, especially in the levosimendan group. After treatment,
LVEDD in each group was significantly lower than that before
administration, but there was no significant statistical difference
between the groups.
The selected HF subjects were patients with significant
impairment of LVEF, so most were admitted repeatedly, the
course of disease was long, and the improvement in cardiac
remodelling was slow. However, the observation time of this
study was short, and the effect of levosimendan on cardiac
structure is not apparent, which could partly explain the results of
comparison of LVEDD between the two groups after treatment.
In addition, the experimental group was given levosimendan
once only, so the long-term efficacy of intermittent repeated
administration of levosimendan needs further study.
Comparing the NYHA grading of the levosimendan and
control groups, the difference was statistically significant. These
results show that levosimendan could improve cardiac function.
No re-hospitalisation occurred in either group within one month
of discharge, indicating that the effect of levosimendan was clear
and it has certain long-term application prospects.
Levosimendan was found to be well tolerated.
28
Its main
side effects included headache (8.7%), hypotension (6.5%) and
hypokalaemia (5%), whereas other treatments include tachycardia
and hypokalaemia as side effects.
29,30
In this study, there were no
significant differences in the values of K
+
, HGB, HCT and Cr
between the levosimendan and control groups before and 48
hours after treatment. During hospitalisation, one patient in the
levosimendan group developed palpitations and was diagnosed
with sinus tachycardia. There was no incidence of hypotension
or severe hypokalaemia in either group. These results suggest
that levosimendan is safe for short-term treatment.
Limitations of this experiment are: (1) the sample size of
this study was relatively small, and the number of cases selected
was limited. A larger study is needed to include more cases. (2)
The follow-up time was short and no further follow up was
carried out. The prognostic effects of levosimendan therefore
need to be further studied. (3) There was no monitoring of
pulmonary capillary wedge pressure, cardiac output, central
venous pressure and other invasive haemodynamic indicators,
Table 6. Comparison of laboratory results between
the two groups before and 48 hours after treatment
Variables
Levosimendan group
Control group
Before
treatment
48 h after
treatment
Before
treatment
48 h after
treatment
Potassium (mmol/l) 4.02
±
0.48 3.96
±
0.43 4.02
±
0.53 3.96
±
0.47
Haemoglobin (g/l) 146.65
±
10.93 146.96
±
13.26 140.35
±
14.02 138.78
±
16.75
Haematocrit (%)
45.06
±
4.32 44.89
±
4.77 42.68
±
4.07 42.35
±
5.53
Creatinine (μmol/l) 81.64
±
24.56 75.14
±
18.16 85.66
±
22.02 85.23
±
17.64