In the presence of non-culprit coronary stensosis, the optimal therapy for that is still a matter of debate. While guidelines discourage a concomitant treatment of infarct- and non-infarct-related arteries, recent studies document advantages of a complete (preventive) revascularization during primary PCI, which may result in overtreatment, as angiography alone does not provide robust information about the functional severity of MVD.
Trang 1FRACTIONAL FLOW RESERVE IN NON-CULPRIT CORONARY ARTERIES OF PATIENTS WITH ACUTE ST ELEVATION
MYOCARDIAL INFARCTION
Vu Quang Ngoc 1 , Ken Kozuma 2 , Nguyen Quoc Thai 1 , Pham Manh Hung 3
1 Vietnam National Heart Institude, Bach Mai Hospital, Hanoi, Vietnam
2 Department of Cardiology, Teikyo University, Tokyo, Japan
3 Department of Cardiology, Hanoi Medical University, Hanoi, Vietnam
Multi-vessel disease (MVD) with stenotic lesions other than the culprit artery (the so-called non-culprit artery) - is present in 40-60% of acute ST elevation myocardial infarction (STEMI) patients, which
is a determintant of higher risk of death and re-intervention compared to single vessel dissease [1] In the presence of non-culprit coronary stensosis, the optimal therapy for that is still a matter of debate While guidelines discourage a concomitant treatment of infarct- and non-infarct-related arteries, recent studies document advantages of a complete (preventive) revascularization during primary PCI, which may result in overtreatment, as angiography alone does not provide robust information about the functional severity of MVD Fractional flow reserve (FFR) measurements have been established in this acute setting as a possibly valuable guide for non-culprit lesions after uncomplicated primary PCI accordingly FFR value ≤ 0.80 has been determined to be predictive of functional significance and, in addition, is the threshold at which revascularisation should be considered The clinical implications of an FFR-guided treatment strategy in STEMI patients with MVD have been proved in a variety of randomized clinical trials CVLPRIT [2], DANAMI-3-PRIMULTI [3] In Vietnam, FFR has been validated in a large number of studies but limited to data of patients with stable ischemic heart disease [4] We undertook the study to assess the FFR of non-culprit arteries in patients with acute STEMI and MVD after uncomplicated primary PCI 81 acute STEMI patients
at 2 institutions (Vietnam National Heart Institute - Hanoi - Vietnam and Teikyo University Hospital - Tokyo
- Japan), who met the inclusion criteria, were enrolled in the prospective, non-randomized study from Nov
2017 to Sept 2018 The mean age was 60.9 ± 12.2 (yrs) 63% of patients were male The most common culprit artery was LAD (57.6%) 60.5% involved 2 vessels, and 39.5% involved 3 vessels Mean percentage diameter stenosis (PDS) was 55.17 ± 9.85% FFR of 135 non-culprit lesions contained of 23.8% lesions with FFR ≤ 0.80, 76.2% lesions with FFR > 0.80 The mean FFR value was 0,82 ± 0,16 The study showed 100% of technical success rate, and 99.3% procedural success rate FFR revealed correlation with minimum lumen diameter (MLD), inverse correlation with lesion length (LL), but no correlation with PDS Measuring FFR of non-culprit artery after uncomplicated primary PCI setting is safe and provides helpful information
on functionally ischemic impact, and further, on revascularization strategy in STEMI patients with MVD
I INTRODUCTION
Keywords: acute myocardial infarction, STEMI, primary coronary intervention, fractional flow reserve.
Acute ST segment elevation myocardial
infarction (STEMI) most commonly occurs
when thrombus formation results in complete occlusion of a major epicardial coronary vessel The most serious form of acute coronary syndromes, STEMI is a life-threatening, time-sensitive emergency that must be diagnosed and treated promptly via primary percutaneous coronary intervention (PCI) to restore blood
Corresponding author: Vu Quang Ngoc, Vietnam
National Heart Institude, Bachmai Hospital
Email: dr.vuquangngoc.cardio@gmail.com
Received: 27/11/2018
Accepted: 12/03/2019
Trang 2flow as soon as possible in the occluded vessel
Multi-vessel disease (MVD) is present in about
40-60% of patients with STEMI referred for PCI,
which is a determinant of higher risk of death and
revascularization compared to single vessel
disease [1] Although the presence of MVD
has been associated with a worse prognosis,
not all studies have shown improved outcomes
when these so called "non-culprit lesions" are
treated with PCI In theory, one might argue
that this is because the lesion in the non-infarct
artery is an "innocent bystander" and therefore
should be approached in much the same
way one approaches stable ischemic heart
disease Opponents to this argument might
propose that these non-culprit lesions may
also be biologically active as there are often
multiple complex plaques in patients with acute
myocardial infarction shown in various studies,
and therefore these arteries warrant treatment
in much the same way one would approach any
unstable lesion There have been a number
of studies including CVLPRIT [2],
DANAMI-3-PRIMULTI [3] which showed benefits of
total revascularization (culprit + nonculprit
artery PCI), but PRAGUE-13 study brought
reverse outcomes Measuring Fractional flow
reserve - FFR in non-culprit coronary lesions
would provide interventional cardiologists
with appropriate information of hemodynamic
significance of the lesions FFR value > 0.80
has been determined to be predictive of
functional significance and, in addition, is the
threshold at which revascularization should be
considered, while FFR value > 0.80 is safe for
conservatively medical treatment In Vietnam,
FFR has been validated in a variety of studies
but limited to data of patients with stable
ischemic heart disease [4] We undertook the
study to assess the Fractional Flow Reserve
in non-culprit coronary arteries of patients with
acute ST elevation myocardial infarction
II STUDY POPULATION AND STUDY METHOD
1 Study population
The study was conducted from Nov - 2017
to Sep - 2018 with 81 consecutive acute STEMI patients who received primary PCI in Vietnam National Heart Institute (n = 31) and Cardiovascular Division - Teikyo University - Tokyo - Japan (n = 50)
Inclusion criteria
• Patient ≥ 18 years old
• Acute STEMI indicated for primary PCI within 12h (from symptoms onset) or > 12h if persistent ischemic demonstration
• At least one non-culprit coronary artery lesion with diameter stenosis of 40% to < 70%
on QCA [5], [6]
• Coronary vessel diameter ≥ 2.0 mm
Exclusion criteria
• Severe heart failure, cardiac shock, Killip III/IV on admission or after culprit coronary revascularization
• STEMI related to in-stent thrombosis
• Unsuccessful primary PCI or complicated primary PCI (inability of stent deployment to culprit vessel, or TIMI flow 0 -
1 post PCI, residual stenosis > 20%, coronary dissection or rupture)
• Non-culprit lesions of < 40% or > 70% of diameter stenosis (on QCA)
• Stenosis of left main stem > 50%
• Non-culprit artery with TIMI flow II
• Chronic total occlusion of non-culprit
• Bypass graft lesions
• Syntax score > 22
• Inappropriate anatomical features for pressure wire passage
• Medical history of allergy to any of the following medication: Aspirin, Clopidogrel,
Trang 3Ticagrelor, Heparin, contrast agents, or
papaverine
• Prolonged bradycardia, AV block, long QT
syndrome
• Anticoagulation disorders or recent history
of bleeding (cerebral, gastrointestinal or
genitourinary) within 3 months
• End-stage renal disease, severe sepsis,
end-stage cancer, or other medical conditions
with estimated life expectancy of less than 1
year
• Pregnancy
• Refuse to enroll in the study
2 Study method
Study design: prospective observational
cohort
Sampling method: non-randomized,
consecutive sampling All acute STEMI
patients with MVD admitted to the National
Heart Institute – Bach Mai Hospital and
Cardiovascular Division - Teikyo University
- Tokyo - Japan, for primary PCI, who are
eligible for study inclusion criteria Non-culprit
coronary lesions were assessed anatomically
by Quantitative Coronary Angiography (QCA)
and functionally by Fractional flow reserve per
protocol [5]
FFR measuring requires the use of a specific PressureWire (solid-state sensor mounted
on a floppy-tipped 0.014- inch guidewire) (St Jude Medical Inc., Minneapolis, Minnesota and Uppsala, Sweden) Before introducing the sensor into the vessel to be studied, the pressures recorded by the sensor and by the guiding catheter should be equalized
A 200 mcg bolus of intracoronary nitrate, followed by papaverine (10mg in the right coronary artery, 20 mg in the left coronary artery LCA), allows the abolition of any form
of epicardial vasoconstriction and hyperemia All procedures were performed during index hospitalization
Statistical Analysis: Continuous variables are presented as mean ± SD or median and inter-quartile range from the 25th to the 75th percentile; categorical data are presented as numbers and percentages, as appropriate
P values smaller than 0.05 were considered
as statistically significant Analyses were performed with SPSS 20.0 (IBM, Inc, New York)
Ethical approval provided by Bach Mai University hospital and Teikyo University hospital
III RESULTS
1 Baseline parameters
From Nov 2017 to Sep 2018 at Vietnam National Heart Institute and Cardiovascular Division
- Teikyo University - Tokyo - Japan, FFR measurements were done on 81 STEMI patients, who received primary PCI, with 135 non-culprit coronary arteries of moderate stenosis (40 - 70% by QCA) Male/female ratio was 1.7/1 The major risk factors included hypertension (67.9%) and smoking (55.6%)
Table 1 Baseline parameters
Trang 4Parameter N
Table 2 Non-culprit coronary artery characteristics
Number of diseased vessel n (%)
2-vessel disease
3-vessel disease
49 (60.5%)
32 (39.5%)
Lesion type n (%)
Type A
Type B1
Type B2
Type C
11 (8.1%)
39 (28.9%)
66 (48.9%)
19 (14.1%)
QCA parameters of non-culprit coronary lesions
Reference vessel diameter - RVD (mm)
Minimal lumen diameter - MLD (mm)
Percentage of diameter stenosis - PDS (%)
Lesion length - LL (mm)
2.88 ± 0.51 1.43 ± 0.27 55.17 ± 9.85 22.45 ± 7.62
2 Fractional flow reserve of non-culprit coronary arteries
2.1 FFR measurement
FFR evaluation were performed via radial access with 6F guiding catheter in a large proportion of patients (96.3%) Femoral access was chosen among 3 cases (3.7%) The time from primary PCI
Trang 5to FFR measurement ranged on an average of 2.65 ± 1.09 days Among 135 non-culprit lesions, the percentage of significantly functional stenosis that required revascularization was 23.8%, while the rest 76.2% of lesions not contributed to physiological impact
The mean FFR value was 0.82 ± 0.09 Lesion distribution was as followed: 22.9% in proximal left descending artery (LAD), 31.3% in the mid LAD, 4.2% in distal LAD, 4.2% in proximal circumflex (LCx), 14.6% in mid LCx, 8.4% in proximal right coronary artery (RCA), 12.5% in mid RCA, and 1.9%
in distal RCA; There was 1 coronary dissection complication related to pressure wire manipulation
2.2 Correlation between FFR and QCA parameters of non-culprit coronary lesions.
Figure 1 Correlation between FFR and PDS.
No significant correlation was found between FFR and PDS
Trang 6MLD was weakly correlated with FFR (r = 0,81, p = 0,04) In other words, the less the MLD, the lower the FFR
Figure 3 Correlation between FFR and lesion length.
Lesion length was moderately inversely correlated with FFR (r = - 0.38, p = 0.045)
III DISCUSSION
Baseline parameters: patients' mean age
was 65.7 ± 12.4 (years) A larger proportion
of patients were male (63%) The major risk
factors include hypertension 67.9%, smoking
55.6% and diabetes mellitus 50.6% Similar
findings were also reported in various studies
[1-3]
The percentage of 2 - vessel disease was
60.5% The complexity of coronary disease was
graded by Syntax score (based on segment
involved, chronic total ccclusion, tortuosity,
angulation, calcification severity, lesion length,
bifurcation ) Syntax score > 22 is known to be
not only an independent predictor of MACEs in
ACS patients with multivessel disease, but also
an indication for early referral to coronary artery
bypass grafting The mean syntax score in our
study was 17.45 ± 2.69 points as only patients
whose Syntax score ≤ 22 were enrolled The
mean RVD was 2.7 ± 0.5 mm and the mean LL was 22.1 ± 7.0 mm
Angiographical characteristics of non-culprit coronary lesions: The complexity of non-culprit coronary lesions was evaluated angiographically based on AHA/ACC 1988 classification, which ranges from type A, type B1, type B2, to type C (the most complex)
A 100% success rate was achieved with pressurewire passage distal to stenotic non-culprit lesions, as most of them were classified
of type A, B1, and B2 The pressurewire was also passed through all 19 complex lesions (type C) thank to unique handling characteristic and flexible tip that in not so much different from regular workhorse wires We reported 1 case
of left main coronary dissection complication related to pressure wire manipulation, which required immediate stent implantation and
Trang 7lead to uncomplicated discharge 2 days after
the procedure In brief, our technical success
rate approached 99.3% The time from primary
PCI to FFR assessment was on the average of
3.14 ± 1.05 days
Correlation between QCA parameters
and FFR of non-culprit artery: In acute
STEMI patients required emergent coronary
angiography, after the culprit artery is
determined with certainty (often based on
the presence of thrombus, no flow or slow
flow at stenotic site ), revascularization and
stent implantation is immediately performed to
restore blood flow to the infarcted myocardial
territory The severity of non-culprit artery
stenosis is then estimated based on visual
assessment, which is commonly applied in
clinical practice This method enables quick
evaluation but subjective and individual-based
decision making While QCA was chosen as
the method of evaluation in our study, PDS
was not shown to be correlated with FFR (r =
- 0.057, p = 0.46) A number of studies stated
weak correlation between the two, but Park et
al [1] found a significantly inversely correlation
Our findings demonstrated a non-significant
difference of PDS between FFR > 0,80 group
and FFR ≤ 0.80 group (p = 0.65) The weak
correlation of PDS and FFR was also mentioned
by Belle et al [6] Data from meta-analysis [7]
suggested that QCA does not help determine
the functional significance in coronary lesions
Although MLD is not a parameter of
choice for interventional cardiologists in their
clinical practice to decide whether or not to
revascularize, our study found the mean MLD
in FFR ≤ 0.80 group was significantly lower
than that of FFR > 0.80 group (p = 0.041)
There was a mild correlation between FFR
and MLD (r = 0.181, p = 0.04), which was also
reported in DANAMI-3-PRIMULTI trial [3] The
smaller the MLD, the lower the FFR value
In our study, lesion length in FFR ≤ 0.80 group was significantly greater than that of FFR > 0.80 group, 24.5 ± 12.5 mm and 17.5
± 8.5 mm respectively (p = 0.016) There was
a moderately reverse correlation between FFR and lesion length with r = - 0.38 (p = 0.045), which showed similar findings in CVLPRIT study [2]
Ntalianis et al [5] investigated the reliability
of FFR of nonculprit coronary stenoses in
101 patients undergoing PCI for an acute myocardial infarction FFR measurements were obtained immediately after PCI of the culprit stenosis and were repeated 35 ± 4 days later The FFR value of the nonculprit stenoses did not change between the acute and
follow-up (0.77 ± 0.13 vs 0.77 ± 0.13, respectively,
p > 0.05) During the acute phase of acute coronary syndromes, the severity of nonculprit coronary artery stenoses can reliably be assessed by FFR This allows a decision about the need for additional revascularization and might contribute to a better risk stratification
V CONCLUSION
In patients with acute STEMI and MVD, FFR measurement after primary PCI appeared
to be feasible and revealed hemodynamic significance of non-culprit artery lesions, which resulted in appropriate multi-vessel revascularization strategy in acute setting
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