Myocardial infarction (MI) due to an isolated side branch (SB) occlusion is a rare clinical presentation. It is often presumed to carry a favorable prognosis compared to main vessel (MV) MI, given the smaller vessel size, lower plaque volume, and smaller myocardial territory at risk, which typically lead to limited ischemia and milder symptoms. Consequently, direct comparative cohort studies are scarce. Most existing research investigates SB occlusion as a complication of MV percutaneous coronary intervention (PCI) or as a challenge in bifurcation stenting, rather than as the primary culprit event. While one can infer that SB MI may have a better prognosis, no large-scale study has explicitly compared the long-term outcomes of patients with primary SB MI versus those with primary MV MI in adjusted cohorts. The purpose of this study was to clarify the clinical characteristics, long-term prognosis, and clinical implications for patients presenting with MI caused solely by an isolated SB occlusion.

We analyzed patient-level merged data from two nationwide, prospective acute MI registries, pooling data specifically from four tertiary PCI centers in Korea. The analysis included patients presenting with de novo, non–left main culprit lesions. Patients who underwent bypass surgery (CABG) during the index procedure were excluded. From a final study population of 4,540 patients, we identified and compared two cohorts: isolated Side Branch MI (SB MI, n = 289, 6.4 %) and Main Vessel MI (MV MI, n = 4,251). The primary endpoint was Target Vessel Failure (TVF), a composite of cardiac death, target-vessel MI, or target-vessel revascularization (TVR). Secondary endpoints included individual components of the primary endpoint and other specific MI and repeat revascularization events. Outcomes were compared using Kaplan-Meier analysis (log-rank test) and multivariable Cox proportional hazards regression, adjusted for baseline clinical and angiographic covariates and stratified by key prognostic factors. Landmark analyses were performed at 6 months to assess early versus late event patterns.

At baseline, patients with SB MI were slightly younger (64 vs. 66 years, p = 0.023) and more likely to be current smokers (38 % vs. 34 %, p = 0.036). Clinically, the SB MI group presented more frequently with NSTEMI (78 % vs. 54 %, p < 0.001), had better left ventricular ejection fraction (LVEF, 58 % vs. 54 %, p < 0.001), and more often had single-vessel disease (69 % vs. 56 %, p < 0.001). Procedurally, SB MI patients were treated more conservatively, receiving fewer stents (59 % vs. 96 %, p < 0.001) and more balloon angioplasty or medical therapy alone.Over 3 years, there was no significant difference in the primary endpoint of TVF (11.7 % vs. 13.4 %; unadjusted log-rank p = 0.261). Landmark analysis confirmed TVF risk was comparable both before and after 6 months. After multivariable adjustment, the initial MI location (SB vs. MV) was not an independent predictor of TVF; risk was driven by traditional factors (hypertension, diabetes, dyslipidemia, and STEMI presentation).However, the SB MI cohort showed a significantly higher adjusted risk for specific late-emerging events: MI from a non-target lesion in the target vessel (Adjusted HR: ~ 4 x) and repeat revascularization for a non-target lesion in the target vessel (Adjusted HR: ~ 2.2 x). Landmark analysis confirmed this excess risk was not apparent in the first 6 months but emerged significantly thereafter, driven by accumulating events in the main vessel.

Isolated SB MI represents a distinct clinical entity. Despite a more favorable baseline presentation, the adjusted 3-year risk for major composite outcome (TVF) is comparable to that of MV MI. This comparable overall risk, however, masks a critical and distinct long-term risk profile: SB MI patients carry a significantly higher late-accumulating risk (emerging after 6 months) for new events originating from the main vessel segment.This finding suggests that a SB-culprit-only approach may be insufficient for long-term safety. The unique temporal risk pattern, potentially signaling underlying main vessel vulnerability, underscores the need for vigilant, tailored long-term surveillance focused on the entire target artery system—particularly the main vessel—in patients presenting with isolated SB MI. Further research is warranted to elucidate the mechanisms of this late risk and establish optimal follow-up protocols.