CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 5, June 2013
AFRICA
169
Discussion
The main finding of the present study was that the appropriate
plasma BNP sampling time that reflected the development of
PMIR in patients with STEMI was the early phase, from two to
five days after the onset of STEMI. Several studies focusing on
the association between plasma BNP and PMIR have confirmed
that elevated BNP is a marker for LV systolic dysfunction and
a significant prognostic marker for morbidity and mortality in
patients with STEMI.
11,12
However, some discrepancies exist in
the optimal time point of plasma BNP sampling that is associated
with the prediction of PMIR.
Some studies reported that plasma BNP levels at one to four
days were strongly related to PMIR after STEMI.
13-15
Other
studies suggested that plasma BNP levels on hospital admission
were associated with PMIR at the six-month follow up in patients
with STEMI.
5,16
One study demonstrated that BNP sampling
three to four weeks after the onset of STEMI was significantly
correlated with PMIR.
7
The results of the present study conflict with several studies
reporting that BNP sampling three to four weeks after the onset
of STEMI was significantly correlated with PMIR. Although
our results showed concordance between plasma BNP levels
at hospital admission and PMIR, plasma BNP levels measured
from two to five days represented a more powerful predictor of
PMIR in patients with STEMI. These discrepancies may have
been due to an inhomogeneous study population, varying time
from symptom onset to reperfusion, reperfusion strategy, infarct-
related arteries, underlying medical conditions, and timing of
BNP measurement.
Plasma BNP level was increased in the acute and early phase
and decreased during follow up in the present study. Plasma BNP
may be synthesised in the ventricular myocardium and released
into the bloodstream in response to multiple stimuli, including
ischaemia, inflammation, ventricular volume overload, pressure
overload, and reperfusion injury.
17,18
Myocardial ischaemia,
the inflammatory response, ventricular volume overload or
pressure overload before reperfusion may occur simultaneously
in patients with STEMI. Importantly, myocardial ischaemia and
inflammatory stimuli can be aggravated by reperfusion during
primary PCI.
19
Microcirculatory obstruction may occur via distal
embolisation, and infarct expansion during PCI may affect the
elevation of plasma BNP levels.
20
Post-PCI plasma BNP level was
consistently higher than pre-PCI plasma BNP level in patients
with STEMI, and those who showed elevated post-PCI plasma
BNP levels were expected to undergo PMIR or cardiac death.
21
Accumulationof intracellular calciumin infarctedmyocardium
before reperfusion does not stimulate or increase the synthesis
and secretion of BNP in the plasma.
22
Even if plasma BNP level
at hospital admission could be a sufficient surrogate marker for
PMIR, it cannot reflect a broad spectrum of myocardial damage,
including reperfusion injury.
Plasma BNP levels after reperfusion in STEMI appeared to be
higher in our study than in several studies on patients with acute
or chronic heart failure.
15,23
Hence, myocardial ischaemia may be
a stronger factor than ventricular volume overload or pressure
overload as a stimulus for BNP secretion. Therefore, ventricular
volume overload or pressure overload before reperfusion may be
non-specific in Killip class I–II or in haemodynamically stable
patients with STEMI.
Plasma BNP level measured from two to five days after
reperfusion correlated not only with ischaemic injury but also
reperfusion injury. This may be important for using post-PCI
plasma BNP level as an integrated biomarker of total myocardial
damage. Also, we demonstrated that plasma BNP level could be
a useful and significant predictor of PMIR that was not inferior
or superior to other established predictors, including age, peak
level of CK-MB and troponin I reflecting infarct size, as well as
echocardiographic LVEF and diastolic filling parameters.
Studies in STEMI and non-STEMI patients have demonstrated
that a biphasic pattern of plasma BNP levels reflects the
major damage to the myocardium and subsequent LV systolic
dysfunction.
4,24
Peak plasma BNP elevations in the present study
were observed in the early phase and long term during the
follow-up periods. Compared with the NRG, plasma BNP levels
were more prominent in the early and long-term phases, so the
pattern of plasma BNP elevation was similar to that observed
in the previous study. Although BNP level three to four weeks
after the onset of STEMI reflecting the second peak of plasma
BNP has been reported,
7
plasma BNP level at six months after
the onset of STEMI appeared to represent the second peak in the
current study.
It has been reported that Doppler-derived E/E
′
,
25
and DT
26
are
relevant measurements of elevated LV filling pressure and LV
dilation in patients with STEMI. We also evaluated and analysed
the diastolic parameters of echocardiography for the prediction
of PMIR. Among the parameters, initial Doppler-derived E/E
′
was significantly correlated with PMIR in a multiple regression
model. Although studies have suggested that Doppler-derived
DT is closely related to the risk of PMIR after STEMI, DT
cannot reflect elevated mean LV diastolic pressure in patients
with preserved systolic function.
25,26
In the present study, plasma
BNP levels at two to five days and initial Doppler-derived E/E
′
proved to be significant predictors of PMIR.
We focused on the background of post-PCI plasma BNP
elevation after successful coronary reperfusion. Although
primary PCI is the optimal therapy in patients with STEMI,
PMIR is a complication that may confound the prognosis.
Post-PCI plasma BNP levels could be affected by myocardial
ischaemia and inflammatory activation that follows reperfusion.
Therefore, we should create an active management plan that
attenuates myocardial ischaemia and inflammatory activation
before and after primary PCI.
The present study had two main limitations. First, this study
had a small sample size of PMIR patients. Second, a distribution
of the infract-related artery and time from symptom onset to
reperfusion was uneven because the clinical situation of each
patient was different.
Conclusion
Elevated plasma BNP level was an independent predictor for
PMIR. The optimal timing of plasma BNP measurement was in
the early phase after the onset of STEMI. We should continue to
use plasma BNP level to define its potential role in monitoring
for PMIR.
References
1.
Tapanainen JM, Lindgren KS, Mäkikallio TH, Vuolteenaho O,
Leppäluoto J, Huikuri HV. Natriuretic peptides as predictors of
