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ACUTE CORONARY SYNDROMES
Left ventricular thrombus formation
after acute myocardial infarction
Ronak Delewi,
1
Felix Zijlstra,
2
Jan J Piek
1
Cardiovascular disease remains the leading cause of
death in western society. Mortality from acute
myocardial infarction (AMI) has decreased since the
introduction of primary percutaneous coronary
intervention (PCI), which has proved to be superior
to thrombolytic therapy by demonstrating lower
mortality rates and reduced clinical adverse events.
Nevertheless, postinfarct complications still lead to
morbidity and mortality in a large number of
patients.
One of the most feared complications is the
occurrence of thromboembolic events (mostly
cerebrovascular accidents) due to left ventricular
(LV) thrombus formation. The risk of LV thrombus
formation is highest during the first 3 months
following acute myocardial infarction, but the
potential for cerebral emboli persists in the large
population of patients with chronic LV dysfunc-
tion. Since these thromboembolic events are
usually unheralded by warning signs of transient
cerebral ischaemia, the only truly satisfactory
medical approach is adequate management of these
high risk groups. This article discusses the inci-
dence, diagnosis and management of LV thrombus
formation after an AMI.
PATHOGENESIS OF LV THROMBUS
The combination of blood stasis, endothelial injury
and hypercoagulability, often referred to as
Virchow’s triad, is a prerequisite for in vivo
thrombus formation. In the presence of LV
thrombus formation after AMI, the three compo-
nents of this triad can also be recognised (fi gure 1).
LV regional wall akinesia and dyskinesia result in
blood stasis, often recognised on two dimensional
echocardiography by the occurrence of spontaneous
LV contrast. Prolonged ischaemia leads to suben-
docardial tissue injury with inflammatory changes.
Finally, patients with an acute coronary syndrome
display a hypercoagulable state with, for example,
increased concentrations of prothrombin, fibrino-
peptide A, and von Willebrand factor, and decreased
concentrations of the enzyme responsible for
cleaving von Willebrand factor (ADAMTS13).
w1 w2
This triad can result in the formation of LV
thrombus composed of fibrin, red blood cells, and
platelets.
LV thrombus can occur within 24 h after AMI.
One study performing serial echocardiographic
studies showed that about 90% of thrombi are
formed at a maximum of 2 weeks after the index
event.
w3
However, some patients develop a new LV
thrombus after discharge, often in association with
worsening LV systolic function. Spontaneous or
anticoagulant induced resolution is relatively
common in LV thrombus formation after AMI.
Thrombus seems to disappear more often in
patients with apical akinesia than those with apical
aneurysm or dyskinesia.
1
It has been speculated that LV thrombus plays
a positive role in the acutely infarcted myocardium,
by offering mechanical support to the infarcted
myocardium and therefore protecting against LV
rupture.
w4
The thrombus becomes firmly attached
to its site of origin, enhancing the underlying
myocardial scar, limiting potential infarct expan-
sion, and partially restoring the thickness of the
myocardial wall. As a consequence, bulging is
reduced, resulting in a more effective myocardial
contraction. Often, however, expansion of the
infarct zone occurs very early after infarction,
before the thrombus has time to organise and is
able to prevent formation of LV aneurysm and
myocardial rupture.
INCIDENCE
Early data from the prethrombolytic and throm-
bolytic eras suggest that in the setting of AMI, LV
thrombus was present in 7e46% of patients, most
frequently in acute anterior or apical myocardial
infarction.
2e4 w3ew5
Differences in diagnostic
techniques, timing of examination and use of
antithrombotic treatment cause substantial varia-
tion in the reported frequency of thrombus from
different series. In addition, it should be noted that
the incidence as reported in autopsy studies is
consistently higher compared with clinical studies,
probably due to better accuracy but also due to
patient selection.
Nowadays the reported incidence is lower. This is
probably due to (1) more aggressive anticoagulation
therapies in the acute phase (eg, the use of heparin,
bivalirudin), (2) smaller infarctions, and (3)
improved LV remodelling. Although the use of ACE
inhibitors is also thought to be associated with
improved LV remodelling, the GISSI-3 study found
no difference in LV thrombus rates between
patients who did and did not receive lisinopril.
5
There are limited data on the exact frequency of
LV thrombus in PCI treated AMI patients. Two
studies found LV thrombus formation in 5.4% and
7.1% of patients with acute anterior wall myocar-
dial infarctions.
w6 w7
However, these studies were
retrospective, non-serial and only assessed LV
<
Additional references are
published online only. To view
these references please visit the
journal online (http://dx.doi.org/
10.1136/heartjnl-2012-301962).
1
Department of Cardiology,
Academic Medical Center,
University of Amsterdam,
Amsterdam, the Netherlands
2
Department of Cardiology,
Erasmus Medical Center,
Rotterdam, the Netherlands
Correspondence to
Professor Dr Jan J Piek,
Department of Cardiology,
Academic Medical Center,
University of Amsterdam, PO
Box 22660, 1100 DD
Amsterdam, The Netherlands;
j.j.piek@amc.uva.nl
Education in Heart
Heart 2012;98:1743–1749. doi:10.1136/heartjnl-2012-301962 1743
thrombus formation at a single point in time and
during the early phase of recovery after myocardial
infarction.
In the latter study a follow-up echocardiography
was performed at 1e3 months, showing LV
thrombus in an additional 8% of the patients.
w7
Solheim et al reported a similar incidence of 15% in
the first 3 months in a selected group of AMI
patients treated by primary PCI.
6
So, the timing of
LV thrombus assessment is crucial, as assessment
too soon after the onset of myocardial infarction
will probably lead to failure to detect the thrombus
in a significant percentage of patients.
CLINICAL FACTORS CONTRIBUTING TO LV
THROMBUS FORMATION
Risk factors for the development of LV thrombus
are consistently irrespective of infarct treatment
and include large infarct size, severe apical asynergy
(ie, akinesis or dyskinesis), LV aneurysm, and
anterior MI.
2 5e8w6
This is consistent with an
increased contribution of at least two of the three
components of Virchow’s triad, namely a larger
area of blood stasis as well as an increased area of
injured subendocardium.
In a study of more than 8000 patients with ST
elevation myocardial infarction (STEMI), LV
thrombus was found in 427 patients (5.1%). This
incidence is relatively low compared to other
studies, probably because of the exclusion of high
risk patients with severe LV dysfunction. Patients
with anterior AMI had a higher incidence of LV
thrombus compared to patients with AMI at other
regions (11.5% vs 2.3%, p<0.0001). The incidence
of LV thrombus was also higher in patients with an
ejection fraction #40% (10.5% vs 4%, p<0.0001).
In patients with an anterior AMI and an ejection
fraction #40% this percentage was as high as
17.8%.
5
Thrombus formation is not exclusively located
apically; approximately 11% occurs at the septal
wall and 3% at the inferoposterior wall.
4
The
prevalence of thrombus in non-anterior myocardial
infarction increases when inferior necrosis extends
towards the posterolateral wall. In such cases the
prevalence is similar to that observed in anterior
wall AMIs of comparable extension.
w5
Thrombi
can also be found in small apical infarcts, with good
global systolic function.
w3
The presence of thrombi is significantly related
to the region of most severe functional impairment
and/or the region with myocardial enhancement
(ie, infarction or scarring).
7
LV thrombus appears
earlier in the course of the disease when initial
ejection fraction #40%, in the presence of multi-
vessel coronary artery disease, or a high peak crea-
tine kinase value.
w8
There is conflicting evidence with respect to the
influence of
b
-blockers. Several studies have
reported a higher frequency of thrombus develop-
ment in patients treated with
b
-blockers which
could be related to the negative inotropic action of
these drugs and thus increased blood stasis. In
particular, in a randomised study, Johannessen et al
reported an increased occurrence of thrombus in
patients with anterior AMI after oral
b
-blocker
therapy.
w9
Turpie et al reported similar results after
treatment with
b
-blockers in a large population of
patients with AMI.
9
The GISSI-2 study, however,
observed the same rate of LV thrombi in patients
with or without atenolol.
10
It has been demonstrated that mitral regurgita-
tion prevents thrombus for mation in patients
with dilated cardiomyopathy.
w10
The protective
effect of mitral regurgitation may be the conse-
quence of augmented early diastolic flow velocities
at the mitral annulus level, as well through the
entire length of the left ventricle, protecting the
LV cavity from a stagnant, thrombogenic blood
flow pattern. In addition, studies suggest abnormal
flow profiles are associated with the presence of an
LV thrombus.
11 w11
However, to date no studies
have demonstrated the same association in patients
with AMI.
There have been few studies on the use of
biomarkers in the setting of LV thrombus forma-
tion. It could be postulated that factors involved in
the coagulation cascade could serve as biomarkers to
identify patients at increased risk for LV thrombus
development. Data presented at the European
Society of Cardiology in 2011 demonstrated higher
soluble tissue factor and d-dimer concentrations in
patients with LV thrombus formation.
w12
Another
study observed mildly elevated anticardiolipin
antibody levels in patients with LV thrombus
formation after AMI.
w13
Whether these factors are
indeed capable of predicting LV thrombus formation
needs to be evaluated.
DIAGNOSTIC MODALITIES TO DETECT LV
THROMBUS
Radionuclide based techniques
In 39 series using radionuclide ventriculography,
a so-called ‘square left ventricle ’ was reported to be
associated with LV thrombus.
w14
The use of
indium-111 labelled platelets is much better docu-
mented. It provides excellent specificity (95%) in
Figure 1 The three components of the Virchow’s triad in
left ventricular thrombus formation. ACS, acute coronary
syndrome; LV, left ventricular.
Education in Heart
1744 Heart 2012;98:1743–1749. doi:10.1136/heartjnl-2012-301962
identifying LV thrombus, and its sensitivity was
reported to be 70% compared with transthoracic
echocardiography (TTE).
w15
It is not applied
widely though because it is time consuming and
expensive, not universally available, and involves
radiation exposure. Furthermore, this scintigraphic
technique is ineffective in identifying relatively
small thrombi, and it has good specificity and
sensitivity only if there is active platelet aggrega-
tion on the surface of the LV mural thrombus at the
time of imaging. In patients with an elevated left
hemidiaphragm, indium-111 activity in the spleen
may be confused with that from the LV apex.
Finally, in patients with a large LV aneurysm but no
LV thrombus, a large amount of relatively static
blood within the LV aneurysm may increase
indium-111 activity.
w16
Echocardiography
Two dimensional TTE is the technique used most
often for assessing the presence, shape and size of
an LV mural thrombus. When the thoracic anatomy
of the patient allows sufficient visualisation of the
heart, two dimensional echocardiography provides
excellent specificity (85e90%) and sensitivity (95%)
in detecting LV thrombus.
12 w17 w18
LV thrombus
on echocardiography is defined as a discrete echo-
dense mass in the left ventricle with defined
margins that are distinct from the endocardium and
seen throughout systole and diastole. It should be
located adjacent to an area of the LV wall which is
hypokinetic or akinetic and seen from at least two
views (usually apical and short axis). Care must be
taken to exclude false tendons and trabeculae and to
rule out artefacts (reverberations, side lobe or near
field artefacts), which constitute the most common
cause for a false diagnosis of a thrombus.
13 14
Another source of false-positive studies result from
tangentially-cut LV wall. Varying gain settings and
depth of field, as well as using transducers with
different carrier frequencies in multiple positions
and orientations, are helpful to minimise such
false-positive studies.
w17
In addition, often the LV apex cannot be clearly
defined and the presence or absence of a thrombus
may be very difficult to establish, leading to an
estimated 10e46% of echocardiograms that are
inconclusive.
w20 w21
Intravenous echo contrast
during TTE may improve the diagnostic assess-
ment of LV thrombus.
12 w22
However, in Europe
the use of most compounds is contraindicated by
the European Medicines Agency in cardiac patients
with acute coronary syndromes, recent PCI, acute
or chronic severe heart failure or severe cardiac
arrhythmias. Also non-protruding and small mural
LV thrombi may still go undetected.
14
Transoesophageal echocardiography (TOE) has
little to offer in the detection of LV thrombus.
Although it is the technique of choice for detecting
atrial masses and thrombi in the left atrial
appendage, its value for diagnosing LV thrombus is
limited because the apex is most often not well
visualised.
12 w23
Nevertheless, some data suggest
that TOE is superior to TTE in providing optimal
visualisation of small LV apical thrombi.
w24
Computed tomography
CTscanning provides about the same specificity and
sensitivity as two dimensional TTE in the identifi-
cation of LV thrombus.
w25
This technique is not
used in daily practice since it requires the intra-
venous injection of radiographic contrast material
and exposes the patient to ionising radiation.
Magnetic resonance imaging
Cardiac magnetic resonance imaging (CMR) with
contrast (delayed enhancement (DE)) has signifi-
cantly better accuracy than TTE and TOE for the
diagnosis of LV thrombus
7 12 w26 w27
(table 1 and
figure 2). A study by Srichai et al compared CMR
and late gadolinium enhancement with echocardio-
graphy in a cohort of patients undergoing LV
reconstruction surgery in whom surgical and/or
postmortem verification of thrombus was
performed.
12
This study reported that the sensi-
tivity of TTE was 40%, compared with 88% for
CMR. Another study reported an echo sensitivity
and specificity of 33% and 91%, respectively, in
a heterogeneous population of patients with LV
systolic dysfunction.
7
These studies reported lower
sensitivity for detection of LV thrombus than
previously described, probably due to exclusion of
suboptimal echocardiographic examinations in the
previously mentioned studies. Also, echocardio-
graphic examinations were often reinterpreted with
emphasis on LV thrombus detection and led to
different findings when the presence or absence of
LV thrombus was based on routine clinical echo-
cardiographic reading as part of the patient’s eval-
uation.
DE-CMR allows for a relatively rapid assessment
of thrombus presence, size, and location and is
nowadays considered the gold standard. The
intravenous administration of gadolinium chelates
greatly enhances the ability to detect and charac-
terise LV thrombi. Immediately after contrast
administration, the homogeneous, strong
enhancement of the LV cavity allows easy detec-
tion of abnormal intraventricular structures (dark),
which frequently occur adjacent to scarred
myocardium (bright hyperenhanced).
Cine-CMR (without a contrast agent such as
gadolinium) seems to be less suitable for LV
Table 1 Sensitivities and specificities of different
diagnostic modalities for the detection of left ventricular
thrombus formation
Sensitivity Specificity
TOE 35% 90%
Routine clinical TTE 35e40% 90%
TTE (indication suspect LV thrombus) 60% 90%
CT Comparable with TTE
Cine CMR 60% 90%
DE-CMR 88% 99%
CMR, cardiac magnetic re sonance imaging; CT, computed tomography;
DE, delayed enhancement; LV, left ventricular; TOE, transoesophageal
echocardiography; TTE, transthoracic echocardiography.
Education in Heart
Heart 2012;98:1743–1749. doi:10.1136/heartjnl-2012-301962 1745
thrombus detection. Thrombus was missed in
44e50% of the cases as detected by DE-CMR.
7 8
The ability of DE-CMR to identify thrombus based
on tissue characteristics rather than anatomical
appearance alone may explain why it provides
improved thrombus imaging compared with cine-
CMR. It should be mentioned that the criteria to
differentiate no-reflow zones from mural thrombi
are not definite, and thus differentiation may not
always be straightforward. Also, further research
and histopathological correlation is needed to
evaluate the role of DE-CMR in differentiating
subacute from organised clots.
Embolic complications
In the prethrombolytic era, embolic complications
were reported in approximately 10% of
cases,
15 w28 w29
whereas in the thrombolytic era,
embolic complications occurred in 2e3% of
patients. There are poor data regarding embolic
complications in LV thrombus patients treated by
primary PCI. Also, exact percentages regarding the
site of embolisation are not available.
Several studies have suggested that LV thrombi
that protrude into the ventricular cavity or that
exhibit independent mobility are associated with
a higher rate of embolisation than thrombi without
these features
16 17 w30
(figure 3). A thrombus is
considered as protruding when it projects predom-
inantly into the LV cavity and as mural when it
appears flat and parallel to the endocardial surface.
Echocardiographic studies analysing mainly retro-
spective and non-serial data have indicated a posi-
tive relationship between the embolic potential of
LV thrombi and their protruding shape and/or
intracavitary motion.
15 w30
However, spontaneous
time-course variation in the morphologic aspects,
such as shape and mobility pattern, are common.
By performing serial echocardiography on 59
untreated patients, Domenicucci et al found that
these morphological features demonstrated
pronounced spontaneous variability in the first
several months after acute infarction, and therefore
suggested that the assessment of these features was
not helpful. They noted that 41% of 59 thrombi
had significant changes in shape and 29% had
changes in mobility.
18
Also, it has been reported
that up to 40% of embolism episodes occur in
patients whose thrombi are neither protuberant nor
mobile.
Other thrombus characteristics, such as
thrombus size,
16
central echolucency
17
or hyper-
kinesia of the myocardial segments adjacent to the
thrombus,
4
were found in some studies to be
associated with an increased risk of embolism, but
were not confirmed by others.
Other conditions that increase the risk of
systemic embolisation are: (1) severe congestive
heart failure, (2) diffuse LV dilatation and systolic
dysfunction, (3) previous embolisation, (4) atrial
fibrillation, and (5) advanced patient age. It has
been suggested that the risk of embolisation is
lower in patients with LV aneurysm, since the
absence of LV contraction near the site of the
thrombus makes dislodgement unlikely.
w31
PHARMACOLOGICAL MANAGEMENT
If indeed systemic embolisation is the highest risk
of LV thrombus, the central question arises as to
how these patients should be treated to prevent
embolisation. In the past, if recurrent systemic
emboli developed despite anticoagulant therapy,
surgical removal of the thrombus was considered
necessary.
17 w31 w32
Nowadays antithrombotic
therapy is thought to prevent embolic complica-
tions of LV thrombus.
Thrombolysis
Vaitkus and Barnathan pooled the data from six
studies comprising a total of 390 patients and
assessed the incidence of LV thrombus formation in
those patients treated with thrombolysis versus
those without thrombolytic therapy. They were
not able to demonstrate a statistical difference in
the incidence of LV thrombus formation, only
a trend in favour of thrombolysis.
19
These studies
Figure 2 Left ventricular (LV) thrombus formation on delayed gadolinium contrast cardiac MRI and transthoracic echocardiography. Transthoracic
echocardiographic appearance of a thrombus (asterisk) in the apex of the left ventricle (A); cine cardiovascular magnetic resonance of the same patient
also delineates the apical thrombus (B); late gadolinium enhancement imaging clearly confirms the avascular non-enhancing thrombus (asterisk, dark)
close to the transmural infarcted myocardium (bright hyperenhanced, black arrowheads) with areas of microvascular obstruction (black, white
arrowheads) (C). Courtesy of Dr A C van Rossum, Dr R Nijveldt, Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands,
and Dr B J Bouma, Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands.
Education in Heart
1746 Heart 2012;98:1743–1749. doi:10.1136/heartjnl-2012-301962
were not randomised but often utilised patients
seen 3 h after symptom onset as a control group.
Data from the GISSI-3 database, including more
than 8000 patients, showed no reduced incidence of
thrombus formation in patients who received
either thrombolytic therapy or heparin.
5
Intravenous thrombolysis has also been used for
treatment of documented LV thrombus. In a report
of 16 patients with LV thrombus on echocardio-
graphy, urokinase was infused intravenously at
a rate of 60 000 U/h for 2e8 days in combination
with intravenous heparin (200 units/kg312 h).
LV thrombi were successfully lysed in 10 of 16
patients. None of the patients suffered from clinical
embolism, and therapy had to be discontinued in
only one patient due to haematuria.
w33
In a later
study, four patients with mobile LV thrombus were
treated with intravenous urokinase or strepto -
kinase. In the first two cases, lysis of thrombus was
achieved without complication. In the latter two
cases, however, systemic embolism occurred, with
transient diplopia in one and stroke followed by
death in the other.
1
It was concluded that fibrino-
lytic agents are capable of lysing ventricular
thrombi but that the risks of this therapy are
too high.
Heparin
Data regarding the benefit of heparin treatment in
patients with documented LV thrombus on echo-
cardiography during the first 2 weeks are somewhat
conflicting, leading us to believe that there may be
a benefit, at least in the short term. In a randomised
controlled trial, AMI survivors who were treated
with high dose heparin (12 500 units subcutane-
ously every 12 h) showed a lower incidence of
LV thrombus formation than those administered
a low dose (5000 units subcutaneously every 12 h)
(11% vs 32%, p<0.001) during a 10 day period.
9
Results from the SCATI study showed a similar
reduction in LV thrombus formation for the group
that was treated with calciumeheparin compared
to the control group in patients undergoing
thrombolysis.
w34
In the GISSI-2-connected study,
however, high dose heparin did not prevent
thrombus formation (27% vs 30%, p¼NS).
10
In
a study with 23 consecutive patients with mobile
and protruding thrombi, high dose heparin was
given intravenously over a period of 14e22 days
(mean 1464). In all 23 patients LV thrombi
decreased in size, with disappearance of the high
risk features. No embolic events were detected
during treatment, and the only complication was
an upper gastrointestinal haemorrhage.
w35
Dalte-
parin, a low molecular weight heparin, reduced the
incidence of LV mural thrombus formation but had
no influence on the risk of systemic embolisation,
and its use was associated with an increased risk of
haemorrhage.
w36
Vitamin K antagonist
Observational studies conducted in the pre-
thrombolytic and thrombolytic eras have provided
support for the hypothesis that anticoagulation
reduces the risk of embolisation.
1 2 4 w3 w37ew39
A 1993 meta-analysis included 11 studies of 856
patients who had an anterior myocardial infarction;
the odds ratio (OR) for an embolic event was 5.5
(95% CI 3.0 to 9.8).
19
The meta-analysis included
seven studies with 270 patients that included data
on the relationship between anticoagulation for
6 months and embolisation. Although all seven
studies presented data suggesting that systemic
anticoagulation reduces embolic complications, this
trend reached significance only in three trials. When
pooling the data, anticoagulation compared with
no anticoagulation was associated with a reduction
in the rate of embolisation (OR 0.14, 95% CI 0.04
to 0.52).
Based on these data, both current European
Society of Cardiology and American College of
Cardiology/American Heart Association guidelines
recommend vitamin K antagonist therapy in
patients with an LV thrombus after myocardial
infarction.
w40 w41
However, vitamin K antagonists do not appear to
affect the likelihood of resolution of the throm-
bus
w3
and, unfortunately, no large randomised trials
have been performed to evaluate the efficacy of long
term anticoagulation to prevent embolisation in
patients with LV thrombus. Therefore the effects of
long term anticoagulants on the risk of embolisation
are the subject of debate. Among the many ques-
tions left unanswered is when to withdraw anti-
coagulant medication when thrombus is identified
since the risk of embolisation decreases over time,
likely as a result of organisation of thrombus which
includes thrombus neovascularisation. However,
retrospective studies documented ongoing embolic
Figure 3 Transthoracic echocardiographic appearance of a mobile, protruding left
ventricular thrombus. Courtesy of J Vleugels and Rianne H A de Bruin, Department of
Cardiology, Department of Cardiology, Academic Medical Center, Amsterdam, the
Netherlands.
Education in Heart
Heart 2012;98:1743–1749. doi:10.1136/heartjnl-2012-301962 1747
risk in LV thrombus patients.
w42
In indium-111
platelet imaging studies most thrombi, regardless of
age, have been observed to have externally detect-
able ongoing platelet accumulation, indicating
continued surface activity.
20
The European guide-
lines recommend vitamin K antagonist for at least
3e6 months, while the American guidelines
recommend indefinite treatment in patients
without increased risk of bleeding.
Although there are limited data regarding the
appropriate follow-up and timing of cessation of
vitamin K antagonists in these patients, the
following approach seems appropriate for most
patients:
<
Assess LV thrombus within the first month
after AMI, preferably with CMR in high risk
patients, and start vitamin K antagonist when
LV thrombus is present and no contraindication
exists
<
Re-evaluate LV thrombus formation after
6 months since data show that LV thrombus
resolution in the initial months is very common,
also in patients treated with vitamin K antag-
onists
w43
<
When LV thrombus is not present and there is
no other indication for vitamin K antagonist,
assess bleeding risk and consider stopping
therapy.
Newer anticoagulants are presently being
developed and some of them are already
registered.
w44ew46
It can be envisioned that in the
longer term these new anticoagulants will replace
vitamin K antagonists. However, at present
vitamin K antagonist therapy is still the standard of
care for the treatment of LV thrombus. More
importantly, the newer anticoagulants also have
the risk of fatal and non-fatal bleedings and their
role in LV thrombus patients should be further
assessed.
Antiplatelet therapy and triple therapy in
the PCI era
Another issue is that nowadays STEMI patients are
treated by primary PCI and receive long term dual
antiplatelet therapy (including aspirin and a P2Y
12
inhibitor). Consequently, patients with LV
thrombus or at increased risk of LV thrombus after
a myocardial infarction are frequently being treated
with vitamin K antagonist in addition to dual
antiplatelet therapy (triple antithrombotic therapy)
and therefore are subjected to an increased bleeding
risk. It is unclear, however, if long term anti-
coagulation is still necessary in STEMI patients
treated by primary PCI and subsequent dual
antiplatelet therapy.
Large prospective studies show a yearly incidence
of bleeding of approximately 3.7% for dual anti-
platelet therapy and 12% for triple antithrombotic
therapy.
w47
The most common site of bleeding is
the gastrointestinal tract (30 e40%) and cerebrum
(9e10%), with 25% of episodes in the latter site
proving fatal. Furthermore, non-fatal bleedings are
an important predictor of mortality post-PCI at
follow-up.
w48
Also, in regard to hospitalisation
Left ventricular thrombus formation after myocardial infarction: key
points
<
Left ventricular (LV) regional wall akinesia and dyskinesia resulting in blood
stasis, prolonged ischaemia leading to subendocardial tissue injury with
inflammatory changes and a hypercoagulable state, are consistent with
Virchow’s triad, resulting in LV thrombus formation.
<
Risk factors for the development of LV thrombus include:
– large infarct sizes
– severe apical asynergy
– LV aneurysm
– anterior myocardial infarction
<
There is reported controversy regarding the negative influence of
b
-blockers
and the protective effect of mitral regurgitation.
<
Early data from the prethrombolytic and thrombolytic era suggest that in the
setting of acute myocardial infarction, LV thrombus was present in 7e46% of
patients.
<
Nowadays the reported incidence is lower, probably due to (1) more
aggressive anticoagulation therapies in the acute phase (eg, use of heparin,
bivalirudin), (2) smaller infarctions, and (3) improved LV remodelling.
<
Timing of LV thrombus assessment is crucial, as assessment too soon after
the onset of myocardial infarction will miss LV thrombus formation.
<
Transthoracic echocardiography is most often used for assessing LV
thrombus. However, it is estimated that 10 e46% of echocardiograms are
inconclusive.
<
Delay enhancement cardiac magnetic resonance imaging (CMR) is nowadays
considered the gold standard.
<
Cine-CMR, transoesophageal echocardiography, radionuclide angiography,
and CT seem less appropriate for LV thrombus detection.
<
Conditions that increase the risk of systemic embolisation in patients with LV
thrombus are: (1) severe congestive heart failure, (2) diffuse LV dilatation and
systolic dysfunction, (3) previous embolisation, (4) advanced age, and (5)
presence of LV protruding or mobile thrombi.
<
Observational studies conducted in the prethrombolytic and thrombolytic eras
have provided support for the hypothesis that warfarin reduces the risk of
embolisation.
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Education in Heart
1748 Heart 2012;98:1743–1749. doi:10.1136/heartjnl-2012-301962
after emergency department visits in the USA for
adverse drug events in patients above 65 years,
33.3% of the 99 628 hospitalisations concerned
warfarin.
w49
Moreover, in the general STEMI
population treated with primary PCI and dual
antiplatelet therapy but no anticoagulation
therapy, symptomatic cerebral infarction is rare,
occurring in 0.75e1.2% of all STEMI patients.
w50
Thus, the potential benefit of vitamin K antagonist
treatment on top of dual antiplatelet therapy may
not outweigh the increased bleeding risk. This calls
for a randomised trial to be conducted to determine
whether anticoagulation treatment prevents
embolic complications in AMI patients treated
with primary PCI.
Acknowledgements We gratefully acknowledge the valuable
contribution of ME Hassell, MD.
Contributors RD: drafting the manuscript; FZ: critical revision; JP:
interpretation of the data.
Funding This work was supported by a grant from the Dutch Heart
Foundation and National Health Insurance Board/ZON MW, the
Netherlands to RD. Grant number 2011 T022 + 40-00703-98-11629.
Competing interests In compliance with EBAC/EACCME guidelines,
all authors participating in Education in Heart have disclosed potential
conflicts of interest that might cause a bias in the article. The
authors have no competing interests.
Provenance and peer review Commissioned; internally peer
reviewed.
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Education in Heart
Heart 2012;98:1743–1749. doi:10.1136/heartjnl-2012-301962 1749
