STEMI Clinical Trial
Official title:
Rheolytic Thrombectomy in Patients With Acute STEMI and Large Thrombus Burden
Coronary obstruction by an occlusive thrombus complicating a ruptured or eroded
atherosclerotic plaque is the most frequent pathologic substrate of acute myocardial
infarction (AMI).
Timely restoration of perfusion and thereby myocardial salvage is the single most important
objective in the management of patients with ST segment-elevation myocardial infarction
(STEMI).
To address these uncertainties, our study aims to evaluate the role of RT in patients who
are most likely to benefit from it (thrombus grade 4 and 5) using a sensitive, quantitative,
and reproducible parameter; CMR-derived myocardial salvage. also, to determine whether
Rheolytic Thrombectomy (RT) before conventional PCI to the culprit vessel as compared to
conventional PCI (with or without MTA) results in improved myocardial salvage; and to
identify clinical and angiographic determinants of any difference observed between both
treatment groups.
Coronary obstruction by an occlusive thrombus complicating a ruptured or eroded
atherosclerotic plaque is the most frequent pathologic substrate of acute myocardial
infarction (AMI) , , . Timely restoration of perfusion and thereby myocardial salvage is the
single most important objective in the management of patients with ST segment-elevation
myocardial infarction (STEMI).
Primary percutaneous coronary intervention (PCI) is now the preferred treatment for STEMI
patients and is effective in opening the infarct-related artery (IRA) and restoring
Thrombolysis in Myocardial Infarction (TIMI) III flow in more than 95% of patients , , .
However the presence of a large thrombus burden increase the incidence of adverse outcomes
including persistent or transient no-reflow and in-hospital major adverse cardiac events
(MACEs), possibly due to distal atherothrombotic embolization, with ensuing disruption of
the microvascular network and failure of myocardial reperfusion . The microvascular
obstruction occurs in 10% of STEMI patients with a patent epicardial vessel after primary
PCI , , . It is associated with an increased infarct size, reduced recovery of ventricular
function, and increased mortality , , , , , , .
Removal of thrombi from the IRA during primary PCI may prevent distal embolization and
improve myocardial perfusion and thus long term clinical outcomes. However studies conducted
to date provide mixed results , , , , , .The two largest randomized trials to date comparing
manual thrombus aspiration (MTA) followed by PCI to PCI only are the Thrombus Aspiration
during PCI in Acute Myocardial Infarction (TASTE) study , and Thrombus Aspiration during
Percutaneous coronary intervention in Acute myocardial infarction (TAPAS) study , . They
further illustrate the existing uncertainties.
TAPAS study showed improvement of the myocardial blush grade (primary endpoint) and
reduction of cardiac mortality at one year follow up in patients of the MTA group compared
to those in the conventional-PCI group. However, it is important to note that TAPAS was not
powered to detect differences in clinical outcome. TASTE study showed no mortality benefit
of MTA at one year follow up. These results concluded that routine use of thrombus
aspiration is not supported by current evidence however, selective use may improve tissue
perfusion in some patients .Accordingly MTA is currently a class IIb recommendation in the
European Society of Cardiology (ESC) guidelines for myocardial revascularization in STEMI
patients , and a class IIa recommendation in the 2013 ACC/AHA STEMI guidelines . The latter
was released before the results of TASTE were published.
MTA is ineffective in ≈30% of patients. Furthermore, residual thrombi after MTA are present
in virtually all patients when studied by optical coherence tomography (OCT).27, . The
currently existing alternative technique for removal of intracoronary thrombi is the
Rheolytic Thrombectomy (RT) by Angiojet device. RT is a catheter-based system that utilizes
multiple high-velocity, high-pressure saline jets introduced through orifices in the distal
tip of the catheter to create a localized low-pressure zone (Venturi-Bernoulli effect),
resulting in a vacuum effect with the entrainment and dissociation of bulky thrombi. The
jets break down thrombi into small particles and propel them proximally through the exhaust
lumen, leading to the aspiration and removal of thrombotic debris without embolization.
The two largest randomized trials to date studying the benefits of RT in patients presenting
with acute STEMI are (JETSTENT) Study and (AIMI) study.
In the JETSTENT study8, ST-segment resolution was more frequently achieved in the RT arm.
There were fewer MACEs (death, MI, target vessel revascularization, and stroke) in the RT
arm at 12 months (p=0.036). Infarct size at one month did not differ between both arms.
However, results of JETSTENT need to be interpreted with caution; in the strict statistical
sense, it was a negative trial. Studies with a co-primary endpoint require a p value of 0.05
for both endpoints or 0.025 for a single endpoint. This was not achieved in JETSTENT.
However, multivariable analysis showed that the use of rheolytic thrombectomy was
independently associated with improved clinical outcomes at one year - acknowledging that
that latter was not one of the primary endpoints.
On the other hand, in the AIMI 24 , the final infarct size was higher in the adjunct RT
group compared to PCI only group. Final TIMI III flow was lower in the adjunct RT group.
Thirty-day MACEs were higher in the adjunct RT group, a difference primarily driven by very
low mortality rates in patients treated with PCI only. There were no significant differences
in TIMI blush grade or ST-segment resolution between both groups. However, there are several
limitations to AIMI; a) the study did not require angiographic evidence of thrombus, and in
fact, excluded patients with very large thrombus burden, b) a retrograde technique - which
involves crossing the lesion before activation of the device - was used in the majority of
patients in the RT group, c) the time delay between admission and use of RT (door-to-device)
was very long, d) compared to the RT group, more patients in the PCI-only group had baseline
TIMI III flow (44% vs. 63%, p= 0.05). Collectively, these factors might have overshadowed
any potential benefit of RT in AIMI.
In another study, Parodi et al 31, compared MTA to RT in patients with acute STEMI using
residual thrombus burden (assessed by OCT) as the primary endpoint. The study did not meet
the primary end point; the number of OCT quadrants containing residual thrombus .However,
angiographic thrombus grade decreased significantly after RT, and all markers of reperfusion
(secondary endpoints) were better in the RT arm. There was a trend toward higher rate of
early ST-segment elevation resolution in the RT arm as compared with the MTA arm. These
findings suggest that RT may be more effective than MTA but to a lesser degree than
hypothesized by the investigators. Furthermore, calculation of thrombus volume by OCT is
extremely challenging given the inability to accurately define the border between disrupted
atherosclerotic plaques and superimposed thrombi, which is further blurred by the optical
shadowing of red thrombus.
To address these uncertainties, our study aims to evaluate the role of RT in patients who
are most likely to benefit from it (thrombus grade 4 and 5) using a sensitive, quantitative,
and reproducible parameter; CMR-derived myocardial salvage. CMR Cardiac MRI can provide a
wide range of information such as myocardial edema (myocardium at risk), microvascular
obstruction (MVO), location and "transmurality" of necrosis, as well as quantification of
infarct size . Moreover, CMR provides accurate and reproducible measurements of ventricular
volumes and function. For these reasons, cardiac MRI is currently perceived as the ideal
tool for evaluation of global post-infarction remodeling.
Myocardial edema in the acute phase of myocardial infarction can be visualized as a bright
signal on T2-weighted images, defining 'myocardium at risk .The major advantages of this
technique are distinguishing chronic from acute infarction, and quantifying the proportion
of myocardial salvage assessed retrospectively by comparing T2-weighted edematous (at risk)
size and late gadolimium enhancement (LGE) images (scar). LGE images are T1-weighted
inversion recovery sequences acquired about 10 min after intravenous administration of
gadolinium and the inversion time is chosen to null myocardial signal using 'inversion time
scout' or 'look locker' sequences .
Delayed post-contrast sequences are currently used also to evaluate persistent microvascular
dysfunction/damage: in the context of white LGE regions (infarcted myocardium) dark
hypoenhanced areas may coexist, traditionally referred to as microvascular obstruction.
Microvascular obstruction has been initially defined as hypo enhancement at 1-2 min after
gadolinium injection; the final infarct size depends mainly on the extent of the so-called
'risk area', defined as the myocardial area related to an occluded coronary artery with
complete absence of blood flow, either antegrade or collateral .
These novel CMR-derived parameters have emerged as potential indices of adverse remodeling,
with the most attractive being myocardial salvage. Myocardial salvage is a prognostically
validated therapeutic target in primary PCI , , , , with myocardial salvage index being a
strong predictor of major cardiac events and mortality at 6-month . Myocardial salvage is
defined as the difference between the initial jeopardized area at risk (determined by
T2-weighted MRI) at baseline and final infarct size (determined by contrast-enhanced MRI).
The myocardial salvage index is defined as final infarct size indexed to the initial area at
risk , , .
Objectives of the study:
1. To determine whether Rheolytic Thrombectomy (RT) before conventional PCI to the culprit
vessel as compared to conventional PCI (with or without MTA) results in improved
myocardial salvage.
2. To identify clinical and angiographic determinants of any difference observed between
both treatment groups.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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