A Diagnostic Paradigm Shift in Acute Myocardial Infarction: Rationale and Design of the DIFOCCULT-3 Trial

Area of Science:

• Cardiology
• Medical Diagnostics
• Clinical Trials

Background:

• Current ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) paradigms have limitations in identifying acute coronary occlusion (ACO).
• Delayed diagnosis of ACO can lead to suboptimal patient outcomes.
• A novel pathophysiology-based strategy is needed to improve ACO detection.

Purpose of the Study:

• To evaluate the efficacy of the occlusive myocardial infarction (OMI) and nonocclusive myocardial infarction (NOMI) paradigm in improving patient outcomes.
• To compare the OMI/NOMI approach against the traditional STEMI/NSTEMI framework for diagnosing acute coronary occlusion.
• To assess if integrating clinical judgment, ECG subtleties, AI, biomarkers, and imaging enhances ACO detection.

Main Methods:

• The DIFOCCULT-3 trial is a multicenter, modified cluster-randomized, open-label study involving 6,000 participants with suspected myocardial infarction (MI).
• The OMI/NOMI approach utilizes clinical gestalt, AI-supported ECG analysis, and adjunctive diagnostics to identify ACO.
• Primary endpoint: composite of all-cause mortality and rehospitalization at 1 year; secondary endpoints include infarct size and ejection fraction.

Main Results:

• Enrollment and follow-up are ongoing.
• Acute outcomes, including earlier ACO identification and infarct size, will be reported post-enrollment.
• Late outcomes, such as mortality and rehospitalization, will be available after 1-year follow-up.

Conclusions:

• The DIFOCCULT-3 study will determine if the OMI/NOMI paradigm offers improved outcomes compared to the STEMI/NSTEMI framework.
• Earlier and more accurate ACO identification is hypothesized to be a key benefit of the OMI/NOMI approach.
• This research could lead to a significant advancement in MI care and diagnostics.