Challenges with the DIFOCCULT Trial

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Would new paradigms result in better patient identification?

Prior to the discovery of thrombolytics, clinicians could only observe their patients completing their myocardial infarctions and then classify them according to whether their subsequent ECGs developed Q waves.


When trials showed a clear survival benefit with thrombolytics (especially in STE) this shifted the paradigm from “Q-wave/non-Q-wave MI” to “STEMI/non-STEMI.” Eventually STEMI became synonymous with acute coronary occlusion (ACO) requiring reperfusion, except this connection was never studied in trials.

Unfortunately, the STEMI criteria have limited diagnostic criteria for ACO, leading to false cath lab activation and worse, missing one-third of ACO (NSTEMI), depriving them of emergent reperfusion therapy. This led many authors to shift from STEMI/NSTEMI to ACO-MI/ non-ACO-MI.

The authors of this newest trial wanted to see if shifting from a STEMI/NSTEMI paradigm to a new approach (ACO-MI/non-ACO-MI) would result in better identification of patients who need acute reperfusion therapy. This was a single center, retrospective case-control study performed in Turkey of patients that presented to the ED with signs and symptoms like ACS.


Based on their presenting ECGs, patients were divided into three groups: STEMI, NSTEMI and control (ACS excluded). The outcomes of significance were the diagnosis of ACO, the sensitivity and specificity of different ECG findings for ACO (up to 48 hours), all cause in-hospital mortality and long-term mortality.

In all there were 1,152 STEMI patients, 2,353 NSTEMI patients, and 15,510 patients with ACS ruled out. With each group, 1,000 patients were included in the final analysis.  The detection of ACO in NSTEMI patients was 28.2%.

Findings on the ECG consistent with this were ST-segment elevation with reciprocal ST-segment depression (76.2%), hyperacute T-waves/de Winter’s patterns (12.4%), subtle anterior ST-segment elevation (6.3%) and non-consecutive ST-segment elevation (4.9%).

When NSTEMI patients were reclassified to ACO, it was found that they were more like STEMI patients than NSTEMI patients:


  • Frequency of ACO: Reclassified NSTEMI (60.9%), STEMI (85.3%), non-reclassified NSTEMI (25.3%)
  • In-Hospital Mortality: Reclassified NSTEMI (5.0%), STEMI (8.3%), non-reclassified NSTEMI (1.8%)
  • Long-Term Mortality: Reclassified NSTEMI (10.6%), STEMI 13.7%, non-reclassified NSTEMI (4.4%)

Using the ACOMI/non-ACOMI approach consistently recognizes high risk subgroups of patients in the NSTEMI population that have a higher frequency of ACO, larger infarct size and higher mortality.

Additionally, it has a superior diagnostic accuracy in the prediction of ACO and long-term mortality compared to the STEMI/NSTEMI approach. More importantly, the ACOMI/non-ACOMI classification does not only depend on the ECG and therefore encompasses a broader category of patients that could potentially benefit from cardiac intervention.

The current STEMI/NSTEMI approach is highly insensitive and has a weak evidence base. It implies that only certain ECG criteria (ST elevations) should be intervened on immediately, missing one-third of ACOs that would benefit from such therapy.  The ACOMI/non-ACOMI approach was also found to improve long-term mortality and has a higher sensitivity, PPV and NPV when compared to the standard STEMI/NSTEMI approach.

Various ECG findings (not just STE) show correlation with ACO and should be used clinically to change the course of management for our patients from observation and troponin trending to the deserved intervention and emergent reperfusion.


Aslanger Emre et al ‘Diagnostic Accuracy of Electrocardiogram for Acute Coronary Occlusion resulting in myocardial infarction (DIFOCCULT Study)     InterJHeartVasc 2020Jul30:30:100603  e collect 2020Oct    PMID 32775606   doi 10.1016/jcha.2020.100603


Dr. Alblaihed is an emergency physician and director of residency education at University of Maryland Upper Chesapeake Medical System.

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