Martina Turk Veselič1
Peri-operative Myocardial Infarction/Injury
after Peripheral Artery Disease Revascularization
ABSTRACT
KEY WORDS: peri-operative myocardial infarction/injury, myocardial injury after non-cardiac surgery,
peripheral artery disease, critical limb ischemia, revascularization, troponin, major adverse cardiovascular
events
The use of a serial high-sensitivity troponin assays enables the diagnosis of a peri-oper-
ative myocardial infarction/injury (PMI), which proved to be a valuable peri-operative
prognostic marker. An absolute increase of post-operative high-sensitivity cardiac tro-
ponin T or I in more than the upper limit of normal above the pre-operative concentra-
tion was associated with an important increase in 30-day and long-term mortality and
cardiovascular events. In patients after revascularization, the incidence of PMI is
approximately 20% which is higher than after non-cardiac surgery in general. Only a minor-
ity of patients with PMI after revascularization have clinical symptoms or ECG changes
suggestive of myocardial ischemia. Therefore, active surveillance is mandatory to prompt-
ly address their residual atherosclerotic risk.
1 Dr. Martina Turk Veselič, dr. med., Klinični oddelek za žilne bolezni, Univerzitetni klinični center Ljubljana, Zaloška
cesta 7, 1000 Ljubljana; martina.x.turk@gmail.com
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INTRODUCTION
The presence of peripheral artery disease
(PAD) confers a three- to six-fold higher risk
for major adverse cardiovascular events
(MACE) compared to the general popula-
tion. The prognosis of patients with criti-
cal limb ischemia is especially poor, with
a 25–% mortality expected in one year. This
may be linked to the presence of concomi-
tant coronary artery disease (presumably in
50–60% patients) (1). Recently, troponin val-
ues before and after a PAD revasculariza-
tion procedure showed to enable peri-pro-
cedural risk stratification that is based on
the detection of so-called peri-operative
myocardial infarction/injury (PMI).
DEFINITION AND
RECOMMENDATIONS
PMI is described as a post-operative high-
-sensitivity cardiac troponin T or I (hs-cTn T/I)
release that indicates acute cardiomyocyte
damage, not necessarily being accompanied
by concordant symptoms, ischemic ECG
changes, or imaging findings. It is defined
as an absolute increase in the hs-cTn T/I
concentration of more than the upper limit
of normal on days one or two after a pro-
cedure. The hs-cTn T concentration com-
plements clinical evaluation and ECG in risk
prediction and is therefore recommended
in patients who undergo high-risk or inter-
mediate-risk procedures, the latter includ-
ing peripheral arterial angioplasty.
Based on emerging data, serial troponin
assessment is advised in the European
Society of Cardiology (ESC) guidelines as
an IB recommendation (2). Symptomatic and
asymptomatic PMI have the same impact
on 30-day mortality.
INCIDENCE AND PROGNOSTIC
VALUE
Large prospective studies have confirmed
the association of PMI with an increased
risk of 30-day and one-year mortality and
non-fatal MACE after non-cardiac surg-
eries. Approximately 16% of high-risk
patients develop PMI. Among those, 30-day
mortality was 8.9% and one-year mortali-
ty was 22.5% (compared to 1.5% and 9.3%
in patients without PMI). PMI is a hetero-
geneous syndrome that can result from var-
ious cardiac and non-cardiac causes.
Invasive coronary angiography was advised
only in 10% of patients being managed for
PMI (3).
In the Puelacher report, only 7% of all
PMI cases were type 1 myocardial infarc-
tion (MI), of those 41% developed clinical-
ly overt MACE and 27% died in one year.
The most common presentation of PMI
was type 2 MI, in this group, 25% of patients
developed overt MACE and 17% died in one
year, compared to 7% and 9%, respective-
ly in non-PMI patients. Other etiologies of
PMI were extra-cardiac, tachy-arrhythmia,
and acute heart failure (4). The baseline hs-
cTn T/I value, when increased, already proved
to be a strong independent predictor of com-
bined cardiovascular endpoints. 
PERI-OPERATIVE MYOCARDIAL
INFARCTION/INJURY AFTER
VASCULAR SURGERY AND
ENDOVASCULAR LIMB
REVASCULARIZATION
There is a discrepancy between different
studies regarding the definition of PMI.
Many are using the term MINS – myocar-
dial injury after non-cardiac surgery – that
excludes cardiac non-coronary aetiology,
the assessment of troponin (I or T, being
high sensitivity) and troponin threshold or
absolute/relative increase values. In a study
that evaluated troponin (that was not high
sensitivity) in patients after lower extrem-
ity revascularization, there was a 23.7%
incidence of MINS after open surgical
revascularization, 19.5% after endovascu-
lar revascularization, and 36% after a hybrid
procedure. Transcriptome profiling analysis
was performed and found gene upregula-
tion for trombospondin 1 that was associ-
48 Martina Turk Veselič Peri-operative Myocardial Infarction/Injury after Peripheral Artery Disease …
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ated with long-term cardiovascular events.
This is only one of possible mechanisms
explaining increased risk in patients with
PAD exhibiting PMI (5).
A study of vascular surgical patients
(after thoracic aorta, aorto-iliac or periph-
eral artery reconstruction, extracranial
cerebrovascular surgery, and endovascular
aortic repair), which defined MINS as an
elevated troponin T value within 30 days
after the operation, found that without
screening, MINS would not be recognized in
74.1% patients. The incidence of MINS
was 19.1%. 30-day all-cause mortality was
12.5% (versus 1.5% in patients without
MINS) and was similar in MINS patients
with and without ischemic feature (6).
In a study that investigated chronic
limb ischemia patients after endovascular
limb revascularization, the incidence of
PMI was 25.5%. The value of hs-cTn T was
determined on admission, three to six
hours after revascularization, and the next
morning. PMI was defined as a hs-cTn T
value above 14ng/L with a relative increase
≥ 30% from the baseline. One year mortal-
ity in patients with critical limb ischemia
that manifested with PMI was 14.2%, and
one year occurrence of MACE was 20.5%.
Interestingly, 62.1% of patients had a base-
line hsTnT value above the threshold level.
Only 14.8% patients with PMI after endovas-
cular revascularization had clinical symp-
toms or ECG changes suggestive of
myocardial ischemia (1).
THE MANAGEMENT OF
PERI-OPERATIVE MYOCARDIAL
INFARCTION/INJURY IN
VASCULAR PATIENTS
A transthoracic echocardiography should be
performed on the day of PMI detection. An
invasive coronary angiography is indicat-
ed in case of type 1 MI or in certain clini-
cal settings of type 2 MI or missed type 1
MI. The last two could also be scheduled for
outpatient stress imaging or coronary CT
angiography. In case of severe anaemia,
other triggers of type 2 MI (such as hypox-
emia, tachycardia, and hypertension), other
cardiac causes (e.g. acute heart failure, aor-
tic valve stenosis) or non-cardiac causes
(e.g. sepsis, pulmonary embolism, stroke)
should be treated (2).
Patients with PAD with confirmed
PMI require even stronger clinical atten-
tion in terms of optimal medical therapy.
Acetylsalicylic acid (ASA) and statins are
already part of their regular the-rapy.
Additional measures are required when tar-
get LDL cholesterol is below 1.4 mmol/L
and at least 50% LDL cholesterol reduction
from baseline are not met (adding ezetimibe
and consequently a proprotein convertase
subtilisin/kexin type 9 (PCSK9) inhibitor)
(7). PAD patients without relevant con-
traindications are candidates for the addi-
tion of a low dose rivaroxaban (2.5mg twice
a day) to ASA according to the VOYAGER
PAD study (8).
Based on the MANAGE study, the addi-
tion of dabigatran 110 mg twice a day may
be considered about one week after non-car-
diac surgery in patients with a low risk of
bleeding as the study showed a 28% rela-
tive reduction of major vascular compli-
cations. Patients who developed MINS
after orthopaedic, general, or vascular
surgery were randomized to receive dabi-
gatran 110 mg twice a day or a placebo
(with initiation six days after operation) and
were followed approximately nine months.
60% of patients already had ASA or an
adenosine diphosphate receptor P2Y12
inhibitor as part of their therapy. The com-
posite primary outcome of vascular mor-
tality, MI, non-haemorrhagic stroke, periph-
eral arterial thrombosis, amputation and
symptomatic venous thromboembolism
was 11% in the dabigatran group and 15%
in the placebo group. There was no differ-
ence in major bleeding (9).
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CONCLUSIONS
PAD patients have significant atheroscle-
rotic burden involving coronary arteries
that predisposes them to a worse cardio-
vascular prognosis. Determining PMI
50 Martina Turk Veselič Peri-operative Myocardial Infarction/Injury after Peripheral Artery Disease …
among PAD patients is beneficial and
should be used as a diagnostic and prog-
nostic tool leading to personalized short-
and long-term post-procedural treatment.
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