This is a single-center, retrospective, observational study conducted at Fondazione Poliambulanza, Brescia, Italy. All consecutive patients were considered eligible for inclusion if they were older than 18 years and had been admitted to the hospital between January 1, 2016, and February 1, 2024, with a diagnosis of STEMI and the culprit lesion located in the LAD. Patients were excluded if they met any of the following criteria:

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  Complex (or unsuitable for QFR analysis) coronary anatomy, namely concomitant chronic total occlusions or surgical grafts, residual ostial disease or side branch involvement in bifurcation lesions, extreme vascular tortuosity and/or intramyocardial bridges.

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  Post-pPCI QFR value < 0.80.

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  TIMI Flow Grade < 3 at the end of the procedure.

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  Out-of-hospital cardiac arrest, cardiogenic shock, or the need for mechanical circulatory support (MCS).

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  Prior STEMI involving the LAD.

Baseline clinical, laboratory, echocardiographic and angiographic characteristics of all included patients were collected.

All patients were treated according to local practice and the best available evidence. Unfractionated heparin was administered for procedural anticoagulation as per standard protocol, while intracoronary nitrates were given at the end of the procedure when feasible. All patients received long-term acetylsalicylic acid (100 mg/day) and a P2Y12 inhibitor for 12 months. Guideline-directed optimal medical therapy was prescribed in accordance with current European Society of Cardiology recommendations.

AngioIMR calculation was performed using the QAngio XA 3D software [Quantitative Flow Ratio (QFR), version 2.2, Medis Medical Imaging, Leiden, Netherlands]. Only the final angiograms- done at the end of the procedure to check the result- were selected if they met technical standards. For each case, QFR was computed from the 3-dimensional vessel’s reconstruction derived from 2 angiographic projections at least 25° apart, while the microvascular assessment was done with the following formula, as previously described:

MAP is the mean arterial pressure; QFR is the pressure ratio virtually estimated with Quantitative Flow Ratio; TFC is the ratio between the number of frames ( N°Frames ) necessary for contrast dye to travel from the coronary ostium to the distal reference and the acquisition rate [ Frames Per Second (FPS) = 15 frames per second], and it was automatically computed by the QFR software. The MAP value was the invasive one recorded by nurses at the end of the procedure, when available. All the analyses were performed by a dedicated physician (C.P.B.), who was unaware of patients’ medical history and in possession of the certification for proper QFR use.

After the index procedure, in-hospital outcomes were collected. Patients were subsequently followed at the hospital’s outpatient clinic, and follow-up data were recorded in the electronic medical record system, from which they were extracted for analysis. When information was unavailable in the system, follow-up was completed via telephone interviews. Follow-up duration was calculated from the index procedure to the last medical contact, and censored at 5 years if longer. The primary endpoint was a composite of all-cause death, target vessel myocardial infarction, or hospitalization for heart failure. The secondary endpoint additionally included hospitalization for angina with no evidence of obstructive epicardial disease at the subsequent angiography. All clinical events were adjudicated by 3 independent reviewers blinded to AngioIMR values. Adjudication was based on review of electronic health records, hospital discharge summaries, and outpatient documentation. Discrepancies were resolved by consensus, and patients were excluded from the analysis in case of missing information.

The distribution of continuous variables was assessed using the Shapiro–Wilk test and visual inspection of histograms. Continuous variables are reported as mean ± standard deviation (SD) for normally distributed data and as median with interquartile range (IQR) for non-normally distributed data. Categorical variables are expressed as absolute numbers and percentages.

Comparisons between groups were performed using the unpaired Student’s t-test for normally distributed continuous variables and the Mann–Whitney U test for non-normally distributed variables. Categorical variables were compared using the χ² test or Fisher’s exact test, as appropriate. A 2-sided p value <0.05 was considered statistically significant.

Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the discriminative performance of AngioIMR, and the optimal cut-off value of AngioIMR was identified using the Youden Index to maximize sensitivity and specificity.

Event-free survival was analyzed using the Kaplan-Meier method and compared between groups using the log-rank test. Cox proportional hazards regression was used to evaluate the association between the optimal binary cut-off value of AngioIMR and the primary endpoint. Variables with p <0.05 in univariate analysis were considered for inclusion in the multivariate model. No imputation for missing data was undertaken, as the variables required for endpoint adjudication and statistical modelling were fully available for all included patients.

All statistical analyses were performed using SPSS software, version 29.0 (IBM Corp., Armonk, NY).

Of the 440 patients who underwent pPCI in the LAD and were initially screened, 180 were ultimately included in the final analysis ( Figure 1 ). A total of 138 patients were excluded due to technical (112 cases) or anatomical (26 cases) constraints limiting QFR computation. In 29 cases, medical records were either incomplete or no longer available within the computer system. Furthermore, at the end of the procedure, 49 patients exhibited less than TIMI 3 flow and 8 patients had a final QFR value below 0.80. Finally, 36 patients presented with out-of-hospital cardiac arrest, cardiogenic shock and/or the need for MCS.

Flowchart illustrating the final cohort of enrolled patients after screening 440 potentially eligible individuals.

Baseline clinical, laboratory, echocardiographic and angiographic findings are summarized in Table 1 , while post-PCI characteristics are shown in Table 2 . The mean age was 64 years, and 83% of the patients were male. The most prevalent cardiovascular risk factors were hypertension (54%) and current or former smoking habit (47%). A small proportion of patients had a history of prior myocardial infarction (8%) or previous PCI (7%). The average left ventricular ejection fraction (LVEF) at presentation- either in the emergency department or upon admission to the coronary care unit- was 40%, improving to a mean of 51% at discharge. Only 12% of patients exhibited severely reduced LVEF (<40%) at discharge. More than half of the cohort had single-vessel disease and presented with complete occlusion (TIMI 0 flow). Total ischemic time was less than 2 hours in approximately 68% of cases, and the mean door-to-balloon time was 53 minutes; only 5 patients (3.2%) received a P2Y12 inhibitor loading dose before angiography. Manual thrombus aspiration was performed in 21% of patients, while a drug-eluting stent was implanted in 177 cases (98%). Plain old balloon angioplasty (POBA) was performed in 2 cases and a drug-coated balloon (DCB) was used in only 1 patient. Glycoprotein IIb/IIIa inhibitors and Cangrelor were administered in 8% and 7% of cases, respectively. The mean postprocedural QFR and AngioIMR values were 0.94 (interquartile range: 0.90–0.98) and 40 (interquartile range: 31–47), respectively. Procedural data are shown in Table 2 . All patients were prescribed acetylsalicylic acid (100 mg/day) indefinitely and a P2Y12 inhibitor for 12 months after the index procedure, while optimal medical therapy was administered according to current guidelines from the European Society of Cardiology.

Table 1

Baseline clinical, laboratory and angiographic findings

	AngioIMR <43 ( n = 106)	AngioIMR ≥43 ( n = 74)	p-value
Age, years	63 ± 14	66 ± 15	0.10
BMI	26.5 ± 4.9	26 ± 3.4	0.39
Male, n (%)	85 (80.2%)	64 (86.5%)	0.27
Hypertension, n (%)	57 (53.8%)	40 (54.1%)	0.97
Diabetes mellitus, n (%)	18 (17.0%)	10 (13.5%)	0.57
Smoking habit, n (%)	52 (49.1%)	32 (43.2%)	0.41
Dyslipidaemia, n (%)	44 (41.5%)	20 (27.0%)	0.057
CKD, n (%)	16 (15.1%)	14 (18.9%)	0.52
Cerebrovascular events, n (%)	2 (1.9%)	2 (2.7%)	0.72
Carotid plaque (>50%), n (%)	12 (11.3%)	7 (9.5%)	0.69
Atrial Fibrillation, n (%)	3 (2.8%)	4 (5.4%)	0.38
Previous MI, n (%)	8 (7.5%)	7 (9.5%)	0.66
Previous PCI, n (%)	6 (5.7%)	6 (8.1%)	0.52
LVEF at admission, %	41.5 [38–46]	40.0 [35–45]	0.089
hsTnI at admission (ng/L)	65 [21–341]	162 [34–1,026]	0.039
TIMI flow 0 at admission, n (%)	63 (59.4%)	43 (58.1%)	0.86
TIMI flow 1 at admission, n (%)	6 (5.7%)	3 (4.1%)	0.63
TIMI flow 2 at admission, n (%)	12 (11.3%)	11 (14.9%)	0.48
TIMI flow 3 at admission, n (%)	20 (18.9%)	16 (21.6%)	0.65
Ischemic time <2 hours, n (%)	78 (73.6%)	44 (59.5%)	0.13
Door-to-balloon time (minutes)	55 (38–66)	49 (34–63)	0.39
Single-vessel disease, n (%)	61 (57.5%)	37 (50.0%)	0.39
Two-vessel disease, n (%)	23 (21.7%)	24 (32.4%)	0.087
Three-vessel disease, n (%)	20 (18.9%)	10 (13.5%)	0.38

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