Ticino Artificial InTelligence integrAtioN for Occlusion Myocardial Infarction

The primary endpoint of the prospective phase, analysed hierarchically using the unmatched, unstratified win ratio, will be a composite of:

• Cardiovascular mortality at 30 days.
• Timely treatment of angiographically confirmed TIMI 0-1 occlusions, defined as insertion of the arterial sheath within 120 minutes from randomization.
• Time-to-treatment of angiographically confirmed TIMI 0-1 occlusions.
• Peak high- hsTnT levels in ng/mL as a surrogate measure of infarct size. Time of coronary intervention will be defined as time from randomisation to insertion of the arterial sheath. Peak hsTnT is defined as the maximum level of hsTnT within 48h from randomization or within 48 hours from intervention if percutaneous coronary intervention took place later than 24 hours from randomization.

Cardiovascular mortality at 30 days

Timely treatment is defined as arterial sheath insertion within 120 minutes of randomization

Expressed in minutes from time of randomization

Peak hsTnT is defined as the maximum level of hsTnT within 48h from randomization or within 48 hours from intervention if percutaneous coronary intervention took place later than 24 hours from randomization.

Major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, or stroke at follow up (30-days, 1 year, 3/5/10 years)

Cardiovascular death at follow up (30-days, 1 year, 3/5/10 years)

Myocardial infarction at follow up (30-days, 1 year, 3/5/10 years)

Stroke at follow up (30-days, 1 year, 3/5/10 years)

• hsTnT area under the curve

• Creatine kinase-MB (CK-MB) peak concentration

• CK-MB area under the curve

Time from randomization to antithrombotic therapy (expressed in minutes)

Time from randomization to coronary angiography (expressed in minutes) This outcome will be assessed both in all patients and in patients with OMI according to the different definitions.

• Worst TIMI flow grade post-PCI (0-3)
• Worst TIMI thrombus grade post-PCI (0-5)

Total time spent in the emergency department post-randomization

Length of hospital stay post-randomization (days)

Number of diagnostic tests and procedures performed post-randomization before coronary angiography, including troponin measurements, transthoracic echocardiography and stress testing

These include both direct and indirect costs.

Direct costs are defined as medical costs incurred post-randomization during the index hospitalization or emergency department visit, including diagnostics and procedures (e.g., ECG, troponin testing, coronary angiography, PCI), medications and consumables, staff time, and length of stay.

Indirect costs, defined as non-medical or societal costs up to 30 days post-randomization, including lost productivity (e.g., time off work for patients or caregivers), transportation to follow-up visits, informal caregiving support, and early rehabilitation services

Restricted to patients in the control group:

• Sensitivity
• Specificity
• Positive predictive value (PPV)
• Negative predictive value (NPV)

Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) instrument at discharge and 30 days post-randomization. The EQ-5D-5L descriptive system comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five levels of severity. Responses are converted into a single index score using a country-specific value set. The index score typically ranges from values below 0 (worse than death) to 1 (full health), with higher scores indicating better health-related quality of life.

Sensitivity analysis of diagnostic accuracy of the AI-algorithm based on the 12-lead ECG recorded immediately prior to the start of coronary angiography, instead of the ECG at presentation.

Sensitivity analysis of the primary outcome using an alternative definition of OMI: TIMI flow 0-1, or TIMI flow 2-3 in the presence of large thrombus burden (TIMI thrombus grade ≥3).