Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT05705102 |
Other study ID # |
MarmaraCard002 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
September 1, 2020 |
Est. completion date |
September 1, 2024 |
Study information
Verified date |
October 2023 |
Source |
Marmara University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The current ST-segment elevation (STEMI)/non-STEMI treatment paradigm misses nearly one
fourth of acute coronary occlusions (ACO) that needs immediately reperfusion. Many of these
cases can be recognized by subtle changes on ECG, but the current STEMI criteria do not
include them. The investigators of this research believe a new occlusive/non-occlusive
myocardial infarction (OMI/NOMI) approach will be superior to the established STEMI/non-STEMI
paradigm in early detection of ACO, limiting infarct size, reducing re-hospitalizations and
most important of all, reducing mortality.
Description:
The patients with acute coronary occlusion (ACO) or potentially imminent occlusion, with
insufficient collateral circulation, have myocardium that is at risk of infarction unless
they undergo immediate reperfusion via thrombolytics or percutaneous coronary intervention
(PCI). One of the most important tasks in emergency cardiology is to immediately identify
acute coronary occlusion (ACO) myocardial infarction (OMI) among all patients who present
with symptoms compatible with acute myocardial infarction (MI), and distinguish them from
those without MI, and from those with MI that does not have ongoing myocyte loss (Non-OMI, or
NOMI) who can be managed with medical therapy and for whom potentially harmful invasive
interventions can be deferred. The electrocardiogram (ECG) plays a central role in this
process.
The presence or absence of ST-segment elevation (STE) is principally used to define patients
who need emergent coronary revascularization, since subgroup analyses of the Fibrinolytic
Therapy Trialists' (FTT) meta-analysis indicated that patients with STE on ECG gain a
slightly better survival benefit from emergent reperfusion. After fine-tuning of STE cutoffs
used in this analysis, universally agreed STEMI criteria became the current
guideline-supported ECG paradigm.
However, the evidence accumulated in the past 20 years indicate that there is still room for
substantial improvement. Although patients with ACO are the group that is believed to benefit
from emergent reperfusion therapy, fibrinolytic studies did not investigate the presence or
absence of ACO among enrolled patients. Moreover, they did not specifically focus on ECG
findings, including STE; four of the nine trials even did not use ECG for enrollment, and the
remaining five defined their version of STE with varying cutoffs, and without specified
measurement methods. To reconcile different STE criteria used in various studies, several
investigators compared STE in normal subjects and patients with MI. However, none of the
studies cited in the current universal definition of MI used ACO on angiography as an
endpoint, so these criteria were actually not designed to differentiate STEMI from non-STEMI.
In the past 20 years, several investigators, including this group, have demonstrated that
factors other than STE, including STE of magnitude less than those recommended by the
guidelines (but in combination with other features), can help in diagnosing ACO or excluding
it. Proportionality, which is unfortunately completely absent in the STEMI criteria, is a
common factor in most of these studies: proportionality is the idea that any amount of STE or
ST-segment depression (STD), or T-wave size, must be assessed relative to the QRS amplitude.
Many other clues should also be taken into account when differentiating STE due to ACO from
other causes of STE, which has been described in detail in recent reviews published by our
group.
Studies show current STEMI criteria miss nearly one-third of ACO with the result that this
unfortunate group of patients, labeled as non-STEMI, are deprived of emergent reperfusion
therapy. Many studies showed that approximately one third to one-fifth of the patients with
ACO had equal to or less than 1 mm of STE, hyperacute T-waves, non-contiguous STE patterns,
etc. These patients are unfortunately deprived of emergent reperfusion therapy and ACO is
only found after rising troponin level identifies them as having MI and they undergo a
next-day angiogram. Furthermore, this proportion may be underestimated, since a large
percentage of total thrombotic occlusions spontaneously reperfuse by this time;
unfortunately, only after a substantial loss of myocardium. These findings are highly
relevant and important, as those with unrecognized ACO had higher short and long-term risk of
mortality.
Recently, the DIagnostic accuracy oF electrocardiogram for acute coronary OCClUsion resuLTing
in myocardial infarction (DIFOCCULT) study [1], compared OMI/non-OMI approach with
STEMI/non-STEMI paradigm. This is the largest study specifically designed to question the
STEMI/non-STEMI paradigm, in which a set of predefined ECG findings in addition to STEMI
criteria were used, and the final outcome was a composite ACO endpoint. In accordance with
the previous observations, over one-fourth of the patients initially classified as having
non-STEMI were re-classified by the ECG reviewers, blinded to all outcome data, as having
OMI. This subgroup had a higher frequency of ACO, myocardial damage, and both in-hospital and
long-term mortality compared to the non-OMI group. The OMI/non-OMI approach to the ECG had a
superior diagnostic accuracy compared to the STE/non-STEMI approach in the prediction of both
ACO and long-term mortality.
Similarly, another retrospective case-control study [2] of 808 patients with suspected acute
coronary syndrome (ACS) symptoms compared the accuracy of STEMI criteria vs. structured
expert ECG interpretation which incorporates other findings of OMI including hyper-acute
T-waves, STD of posterior OMI, STE less than the STEMI criteria cutoffs, etc. STEMI (-) OMI
patients had similar infarct size measured by peak troponin but greater delays to angiography
compared with the STEMI (+) OMI patients. Of the 808 patients, 49% had MI (33% OMI; 16%
NOMI). Sensitivity, specificity, and accuracy of STEMI criteria vs Expert 1 for OMI among all
808 patients were 41% vs 86%, 94% vs 91%, and 77% vs 89%, and for Expert 2 among 250 patients
were 36% vs 80%, 91% vs 92%, and 76% vs 89%. OMIs were correctly diagnosed a median of 1.5
hours (mean 3.0 hours) earlier by structured expert ECG interpretation than by STEMI
criteria, or by angiogram if the ECG never met STEMI criteria.
Lastly, the STEMI/NSTEMI vs. OMI/NOMI paradigm were compared in 467 consecutive high/risk
acute coronary syndrome patients [3]. Among the 108 patients with OMI, only 60% had any ECG
meeting STEMI criteria. STEMI (-) OMI patients had similar peak troponins, wall motion
abnormalities, left ventricular ejection fraction (LVEF) and clinical outcomes as compared
with the STEMI (+) OMI patients, but were much less likely to receive emergent
catheterization.
These data support the notion that the STEMI (-) but OMI (+) patients likely represent a
missed opportunity under the STEMI/NSTEMI paradigm. A new OMI/NOMI approach has the potential
of being the next significant improvement in modern MI care.
The hypothesis of this study is that the new OMI/NOMI approach will be superior to the
established STEMI/NSTEMI paradigm in early detection of ACO, limiting infarct size, reducing
rehospitalizations and most important of all, reducing mortality.
The adult patients (age >18 years) who are admitted to the emergency department with a
clinical picture compatible with acute coronary syndrome will be screened for enrollment into
the study. If any ECG in the emergency department is recognized as OMI/STEMI (according to
the treating provider) or if the troponins are elevated, the patient will be enrolled into
the study.
Before the study a detailed briefing will be done to the interventional cardiologists who
will form the intervention groups.
Although the STEMI/NSTEMI approach is the current norm (a diagnosis of STEMI requires
emergent catheterization, whereas the patients with NSTEMI are stabilized first and then
electively undergo catheterization unless there are high-risk features), it would be
unethical for a ECG reviewer, who is trained in recognizing the signs of ACO not fulfilling
the current STEMI criteria, to suspend emergent reperfusion therapy after an OMI diagnosis
has been made. Therefore, the ECG interpreters who are trained in OMI diagnosis cannot be
randomized to STEMI/NSTEMI versus OMI/NOMI approaches. Hence, the groups will be randomized
in the following fashion: A OMI/NOMI and a STEMI/NSTEMI intervention group will be formed.
Intervention group 1 will be encouraged to use OMI/NOMI approach in patients with suspected
acute coronary syndrome, and group 2 will use the current STEMI/NSTEMI approach.
The ECG interpreters (who contact the patient first and decide the treatment style, according
to the center this can be either an emergency physician or a cardiologist) in both groups
will be ensured to have a similar experience in terms of years of training. The ECG
interpreter will thus elect to go for catheterization based on his/her ECG approach and,
whether that is by OMI or STEMI paradigm, the patient will be enrolled accordingly and the
reason for proceeding to the catheterization laboratory will be written on the study form.
The interventional cardiologists in both groups will be ensured to have a similar experience
level (in terms of years of training, and angiography and primary PCI counts in the past
year). In the STEMI/NSTEMI arm, the contributors will blindly continue their practice, the
ECG interpretation and decision to activate the catheterization laboratory will be done as
usual. In the OMI/NOMI arm, an intensive course on ECG diagnosis of OMI using previously
published algorithms and ECGs will be provided [4, 5]. After these two groups are formed, the
patients will be block-randomized into STEMI/NSTEMI and OMI/NOMI cohorts according to the
team on-duty. No intervention to the decisions will be done during the study process.
The STEMI/NSTEMI group will use the following criteria for the diagnosis of STEMI: (1) New
ST-segment elevation at the J-point in two contiguous leads with the cut-point: ≥ 1 mm in all
leads other than leads V2-V3 where the following cut-points apply: ≥2 mm in men ≥40 years;
≥2.5 mm in men <40 years, or ≥1.5 mm in women regardless of age, and (2) a peak troponin
level above 99th percentile and (3) a clinical picture compatible with acute coronary
syndrome. If the decision to proceed to the cath lab was done only with the first criterion,
the participant will remain in the study, even if the second criterion is not met. The
patients meeting only criteria (2) and (3) will be classified as NSTEMI.
In the OMI/NOMI group, the algorithm defined in the DIFOCCULT trial [1, 4, 5] will be used
for ECG diagnosis (1). Additionally (2) a peak troponin level above 99th percentile and (3) a
clinical picture compatible with acute coronary syndrome will be required. If the decision to
proceed emergently to the cath lab was done only with the first criterion, the participant
will remain in the study, even if the second criterion is not met. The patients who do not
meet ECG-OMI criteria will be classified as NOMI, if: (1) a peak troponin level above 99th
percentile and (2) a clinical picture compatible with acute coronary syndrome is present.
STEMI and OMI patients (will be taken as STEMI equivalents) will be managed according to the
current STEMI guidelines, whereas NSTEMI and NOMI patients are managed according to the
current NSTEMI guidelines. A separate diagnostic group with 'probable OMI' and 'high-risk
STEMI' is also allowed for patients who do not fulfil STEMI/OMI criteria but need urgent
catheterization for other high-risk features or high clinical suspicion for having an ACO.
These patients will also be managed according to the current guidelines. However, patients
will be excluded from analysis if their early catheterization is based solely on social or
logistical considerations, and not based on the medical need. For example, a patient would be
excluded if he/she is brought to the cath lab early based on the immediate availability of
cath lab or because the patient is already scheduled for elective coronary angiography.
No other intervention will be done during study. After the patient enrollment period, data
will be retrieved from the system and will be compared.