Emre K Aslanger, Burcu Aggül, Özlem Yıldırımtürk, Can Yücel Karabay, H. Pendell Meyers, Stephen W. Smith, Muzaffer Deǧertekin, Belma Kalaycı, A N Erdem, Havva Tuğba Gürsoy, Ahmet Akdi, Sinan Cemgil Özbek, V O Tanık, Arzu Neslihan Akgün, Ertan Ekici, Gürbey Söğüt, Tolgahan Efe, Ayşenur Özkaya İbiş, Çağatay Tunca, Y Oz, İbrahim Halil UYGUN, Buse Çuvalcıoğlu, Muhammed Aydın, Ezgi Polat Ocaklı, Tuğba Kayhan Altuner, Dursun Akaslan, Murat Esin, Burcu Ozyazgan, Aydin Ih, Ali Oğuzhan Karal, Esra Dönmez, Sevgi Özcan, O Ince, Muhammed Furkan Deni̇z, Irfan Sahin, Abuzer Coşkun, Mustafa Rauf Karayumak, Ersin İbişoğlu, Uğur Ozan Demirhan, Aslan Erdoğan, Eyüp Özkan, İlyas Çetin, Yusuf İnci, S S Kalkan, Ufuk Yıldız, Said Kural, Tuba Danacı, Burcu Kırbıyık, Merve Işık, Utku ULUKÖKSAL, Furkan Fatih Yücedağ, Elif Ozoguz, Oktay Seker, Barış Yaylak, Ufuk Sadık Ceylan, Gönül Zeren, Mustafa Azmi Sungur, Mehmet Fatih Yılmaz, Tolga Onuk, Oğuzhan Birdal, Sidar Şiyar Aydın, E TEKIN, Emrah İlkay Varınca, Ezgi Çamlı Babayiğit, Halit Emre Yalvaç, E Sener, Hazal Tiraş, Barış Özden, Ayberk Beral, Kadir Uğur Mert, Gurbet Özge Mert, Cihat Çalışkan, Azmican Kaya, Metehan Kibar, Mustafa Furkan Kılıçarslan, Emre Kipritçi, Seyma Zeynep Atici, Simay Erdal, Sedat Kalkan, Çetin Geçmen, Muzaffer Kahyaoğlu, Mehmet Aytürk, Mevlüt Demir, Taner Şen, Halil İbrahim Durmuş, Emrah Kaya, Fatih Kahraman, Celal Kılıt, M A Astarcioglu, Veysel Elitas, Yakup Han Yilmaz, Uğur Güven, Zekeriya Doğan, Eren Uysaler, Ahmet Cem Nizam, Tansu ÇELİK, Ebrunur Türkmen, B Çavuş, Fevzi Sünbül, Sena Nasif
BACKGROUND: The current ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) paradigm have long been the cornerstone of myocardial infarction (MI) care but fail to identify many patients with acute coronary occlusion (ACO), delaying treatment and worsening outcomes. OBJECTIVES: The new occlusive MI (OMI) and nonocclusive MI (NOMI) paradigm addresses these limitations by shifting from rigid electrocardiography (ECG)-driven thresholds to a pathophysiology-based strategy. It integrates clinical judgment, ECG subtleties, supportive artificial intelligence, biomarkers, and imaging when needed to actively detect ACO. The current trial investigates whether this approach improves outcomes. METHODS: The DIFOCCULT-3 (Time for a DIagnostic paradigm shift from ST-elevation/non-ST-elevation to OCClUsion/non-occLusion myocardial infarcTion? trial is a multicenter, modified cluster-randomized, open-label study designed to compare the OMI/NOMI paradigm with the STEMI/NSTEMI approach in 6,000 participants presenting with suspected MI. The OMI/NOMI approach integrates clinical gestalt, artificial intelligence-supported ECG analysis, and adjunctive diagnostic tools to actively identify ACO. The primary endpoint is the composite of all-cause mortality and all-cause rehospitalization at 1-year follow-up. Secondary endpoints include infarct size, left ventricular ejection fraction, wall motion score index, and accurate diagnosis of ACO. RESULTS: Enrollment and follow-up are ongoing; acute outcomes such as earlier identification of ACO and infarct size will be reported after enrollment, and late outcomes including mortality and rehospitalization will be available after 1-year follow-up. CONCLUSIONS: The DIFOCCULT-3 study aims to determine whether the OMI/NOMI paradigm represents a significant advancement in MI care by improving outcomes through earlier and more accurate identification of ACO than the STEMI/NSTEMI framework (Time for a Diagnostic Paradigm Shift From STEMI/NSTEMI to OMI/NOMI [DIFOCCULT-3]; NCT06570759).